Cancer Research and Treatment

Volume 32(1); February 2000

Original Articles

The Incidence of Hereditary Gastric Cancer in Korean: Soo Jin Kim, Sam Je Cho, Seung Chul Heo, Han Kwang Yang, Woo Ho Kim, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(1):1-6.

Abstract PDF: PURPOSE
We wanted to determine the incidence of HGC (hereditary gastric cancer) in Korean under the minimal criteria of ICG-HGC (International Collaborative Group on Hereditary Gastric Cancer).
MATERIALS AND METHODS
Tumor registry abstracts of 1752 patients who underwent operations for gastric cancer during the time period 1996 to 1998 in the Department of Surgery at Seoul National University College of Medicine were examined. Based on their family histories, candidate HGCs were identified. Their detailed family histories including diagnosis of cancer, age at diagnosis, and dates of birth and death were obtained from interviews by phone. Another study was performed on 195 patients with gastric cancer who admitted for operations in the same department during the time period April, 1999 to June, 1999. Their detailed family histories were also obtained from probands or nearest relatives during admission. Pedigree studies of documented families were conducted. Minimal Criteria of ICG-HGC we used for present study are as followings: At least three relatives with histologically verified gastric cancer; one of them should be a first-degree relative to the other two. At least two successive generations should be affected. In one of the relatives, gastric cancer should be diagnosed under 45 years of age. Suspected HGC fullfills only two of the above three criteria. HNPCC, FAP and Li-Fraumeni syndromes should be excluded.
RESULTS
A total of 12 HGCs were identified in this study. In recent 3 years, during the time period 1996 to 1998, the incidence of true and suspected HGC accounted for 6 (0.3%) and 44 probands (2.5%) among 1752 patients (in 1996, 0.4% and 3.2%; in 1997, 0.3% and 1.8%; in 1998, 0.3% and 2.8%) respectively. In contrast, during the time period April, 1999 to June, 1999, the incidence of true and suspected HGC increased up to 3.1% (6 probands) and 11.3% (22 probands), respectively, out of 195 patients (in April, 1999, 0% and 11.7%; in May, 1999, 4% and 14.7%; in June, 1999, 5% and 6.7%). There was no difference in terms of the incidence even if the third criterion of age at diagnosis among Minimal Criteria of ICG-HGC was modified from 'under 45 years of age' to 50. Mean ages of 12 probands (46.3 8.8) were statistically younger than those of control gastric cancer patients (54.2 11.5) retrieved from database of Department of Surgery at Seoul National University College of Medicine.
CONCLUSION
In the present study, the incidences of HGC were remarkably altered in accordance with study methods. Retrospective reviews of medical records revealed to be ineffective for this kind of study since their informations were often incomplete and some suspected patients were lost during follow-up. According to the Minimal Criteria of ICG-HGC, the incidence of true and suspected HGC was 3.1% (6 probands) and 11.3% (22 probands), respectively, out of 195 gastric cancer patients. We propose that families who meet the Minimal Criteria of ICG-HGC should be prospectively found in order to determine the exact incidence of HGC in Korean.

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Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment: Yong Wha Moon, Hoon Yang, Hei Chul Jung, Sun Young Rha, Tae Soo Kim, Nae Choon Yoo, Sung Hoon Noh, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):7-18.

Abstract PDF: PURPOSE
Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography.
RESULTS
MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor.
CONCLUSION
We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.

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Tumor Angiogenesis as a Predictor of Malignancy Potential and Prognosis in Gastric Carcinoma: Chang Wuk Kang, Hyung Ho Kim, Young Hoon Kim, Se Heon Cho, Sang Soon Kim, Mee Sook Roh, Suk Hee Hong, Choong Rak Kim; J Korean Cancer Assoc. 2000;32(1):19-25.

Abstract PDF: PURPOSE
In order to evaluate the clinical relevance of angiogenesis in patients with gastric cancer, we investigated the microvessel count in gastric cancer tissues and compared the results with several clinicopathologic factors and prognosis.
MATERIALS AND METHODS
A total of 256 patients with gastric cancer who underwent curative surgery were included in this study. Microvessel count was determined by im-munohistochemical staining using monoclonal antibody against factor VIII-related antigen.
RESULTS
The statistical significance between the microvessel count and clinicopathologic factors (age, sex, tumor invasion, lymph node involvement, histologic type) was analized. The tumor stage and histologic type were correlated with microvessel count. And also there was statistical significance with survival rate and recurrence-free survival rate between high (microvessel count> or =42) and low angiogeneic group (microvessel count< 42). The Cox's proportional hazard model showed that stage, histologic type, angiogeneic score were one of the significant and independent prognostic variables.
CONCLUSION
The tumor angiogenesis of gastric carcinoma may be independent prognostic factor for predicting recurrence and survival.

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Clinicopathologic Characteristics and p53, c-erbB2, nm23 Protein Expression in Gastric Remnant Cancer: Joo Ho Lee, Yoe Kyu Youn, Woo Ho Kim, Hang Jong Yu, Byoung Jo Suh, Han Kwang Yang, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(1):26-37.

Abstract PDF: PURPOSE
The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer.
MATERIALS AND METHODS
We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23.
RESULTS
The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC.
CONCLUSION
Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.

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The Significance of Serum CA 19 - 9 Level in Gastric Adenocarcinoma: Yong Jin Kim, Byung Sik Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sun Suh, Wan Soo Kim, Yong Ho Kim, Kun Chun Park; J Korean Cancer Assoc. 2000;32(1):38-43.

Abstract PDF: PURPOSE
This study was designed to investigate the significance of preoperative serum CA 19-9 level as a prognostic factor and postoperative serum CA 19-9 level as an indicator for recurrence in gastric adenocarcinoma patients.
MATERIALS AND METHODS
328 patients, who received curative resection of stomach for gastric cancer from 1989 to 1996 and followed up successfully, were analyzed retrospec- tively. Median follow-up period was 24 months (range: 11-38 months). The cut off level of serum CA 19-9 was 37 U/ml. The relationships between preoperative serum CA 19-9 status and prognostic parameters, recurrence and survival rate were analyzed. Multivariate analysis using Cox proportional hazards regression analysis was performed to evaluate as an independent prognostic factor. The relationship between postoperative serum CA 19-9 level and recurrence was investigated.
RESULTS
Out of 328 cases, 29 cases (8.8%) showed elevated preoperative serum CA 19-9 level. The preoperative serum CA 19-9 level was correlated with the degree of depth of invasion and the status of lymph node metastasis (p<0.05). Patients with positive pre- operative serum CA 19-9 status showed higher incidence of recurrence (p<0.05) and poorer survival rate (p=0.00003) than patients with negative status. Preoperative serum CA 19-9 status (risk ratio: 3.4464, p=0.0039) revealed as an independent prognostic factor in multivariate analysis. Postoperative serum CA 19-9 status revealed as a useful predictor for recurrence in patients with positive preoperative serum CA 19-9 status.
CONCLUSION
Preoperative serum CA 19-9 determination in patients with gastric cancer was valuable for predicting tumor progression and prognosis. Preoperative serum CA 19-9 status may be helpful to predict recurrence earlier than other diagnostic tools, especially in the patients with positive preoperative serum CA 19-9 status.

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Drug Resistance to 5 - Fluorouracil and Overexpression of Thymidylate Synthase mRNA in Human Gastrointestinal Malignancies: Tae You Kim, Baek Yeol Ryoo, Yung Hyuck Im, Yoon Koo Kang, Sang Jae Lee, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 2000;32(1):44-52.

Abstract PDF: PURPOSE
The cytotoxicity by 5-fluorouracil (5-FU) is mediated by inhibition of thymi- dylate synthase (TS), which is a rate-limiting enzyme for DNA synthesis. To test whether the resistance to 5-FU would be associated with cellular TS activity, we analyzed TS gene expression from human gastrointestinal cancer cell lines.
MATERIALS AND METHODS
We established the experimental conditions for quantitating TS mRNA expression by competitive RT-PCR using mimic DNA. Based on this method, we compared TS mRNA expression between 5-FU resistant cell line and parent cell line and investigated the expression of TS mRNA following 5-FU administration in 6 human gas- trointestinal cancer cell lines.
RESULTS
Competitive RT-PCR using mimic DNA seemed to be more effective than Northern blot analysis for quantitation of TS gene expression. The quantity of TS mRNA and IC50 value of 5-FU in 5-FU resistant H630 was found to be 2.5 and 10 times higher than in parent cell line, respectively. And also, we observed linear relationship between TS mRNA level and IC50 value of 5-FU (r 0.76) in 6 gastrointestinal cancer cell lines.
CONCLUSION
These results suggest that overexpression of TS mRNA may play a role in the development of 5-FU resistance in human gastrointestinal malignancies

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Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues: Soo Jung Gong, Sun Young Rha, Hei Chul Jung, Joon Oh Park, Nae Choon Yoo, Jae Kyung Roh, Woo Ick Yang, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):53-59.

Abstract PDF: PURPOSE
Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients.
MATERIALS AND METHODS
Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients.
RESULTS
The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

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Expression Pattern and Prognostic Correlation of BAG - 1 Protein in Breast Cancer: Se Hoon Cho, Dae Young Lee, Byung Jin Kim, Sook Hee Hong; J Korean Cancer Assoc. 2000;32(1):60-67.

Abstract PDF: PURPOSE
The objective of this study was to understand the expression of BAG-1 in the human breast cancer.
MATERIALS AND METHODS
We studied its expression in one hundred and thirteen patients diagnosed with breast cancer in Dong-A university hospital between 1992 and 1996 by performing immunohistochemical staining with BAG-1 monoclonal antibody.
RESULTS
Of the 113 breast carcinoma examined, 62.0% were positive for BAG-1 cyto- plasmic expression, 28.0% were positive for nuclear BAG-1 expression and 9.7% were positive for both BAG-1 cytoplasmic and nuclear expression. The higher histologic grade was correlated with the higher cytoplasmic expression (p<0.05). Except for histologic grade, no correlation was observed between BAG-1 expression and conventional prognostic factors such as age, menopausal status, metastatic status of the axillary lymh nodes, cathepsin-D, p53, C-erbB-2, DNA ploidy, S-phase fraction, PCNA (proliferating cell nuclear antigen). CONCLUSION: The high histologic grade was found to correlate with positive BAG-1 cyto- plasmic staining which did not correlate with conventional prognostic factors. Our data indicate that furthermore investigation is warranted to define the role of BAG-1 as an meaningful prognostic factor in patients with newly diagnosed breast cancer.

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Personal Experience of 1,000 Breast Cancer Surgeries in Korea: Sei Hyun Ahn; J Korean Cancer Assoc. 2000;32(1):68-75.

Abstract PDF: PURPOSE
A specialized breast surgeon is important to give comprehensive treatments to breast cancer patients. The purpose of this study was to evaluate the characteristics and treatment results of breast cancer patients in my breast clinic, and to share the experience of clinical management and data base recording and its clinical use.
MATERIALS AND METHODS
I had performed 1,018 breast cancer surgeries from Mar. 1992 to Mar. 1998 at the Breast Clinic in Asan Medical Center.
RESULTS
The results were as follows; 1,008 cases were female (99.0%), and 10 cases were male (1.0%). The peak incidence was in 40~49 years of age (36.5%), followed by 30~39 years (24.0%) and 50~59 years (23.3%). 647 cases (63.6%) were under the age of 50. The most common operative method was a modified radical mastectomy in 747 cases (73.4%), and breast conserving surgery was performed in 173 cases (17.0%). Immediate breast reconstruction was performed in 63 cases (tissue expander with implant in 50 cases, direct implant in 4 cases, TRAM flap in 8 cases, and LD flap in one case), and SSM (skin-sparing mastectomy) through circumareolar incision was done in 9 cases. According to TNM classificasion, the most common was stage II in 49.2% (501 cases), and the proportion of early-breast cancer (stage 0 and I) was 33.7%. The axillary lymph node metastasis was present in 43.5%. The 5-year overall survival and disease free survival rate was 81.4% and 70.7%. There was no local recurrence in breast conserving surgery by median follow-up of 32 months.
CONCLUSION
As a breast surgeon, I have tried to apply the appropriate operation methods according to the patients condition. The survival data was fairly good, and there was no local recurrence after breast conserving surgery yet. Data computerization was very useful for evaluating the characteristics of the patients.

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The Significance of Bone Marrow Micrometastasis ( BMM ) in Breast Carcinoma: Su Hwan Kang, Soo Jung Lee, Sang Woon Kim, Koing Bo Kwun; J Korean Cancer Assoc. 2000;32(1):76-85.

Abstract PDF: PURPOSE
This study was performed to determine the incidence of BMM and to correlate the presence of these micrometastases with prognosis and othet clinicopathologic features.
Materials AND Methods
BMM was evaluated in 220 breast cancer patients between July, 1991 and January, 1997, using mouse monoclonal antibody (AE1/AE3) against cytokeratin in an immunofluorescent assay.
RESULTS
Of the 220 patients, 71 (32.3%) were positive for BMM. There were no association between bone marrow positivity and nodal status, TNM stage, known histopathologic parameters, and hormona1 receptor. Median follow-up for 220 patients was 41.6 month. The relapse rate was 16.8% (37/220). Twenty-four (33.8%) of 37 patients were positive for BMM and 13 (8.7%) were negative (p<0.05). Bone metastasis occurred in 16 cases, and was more common in BMM positive patients (14 of 24, 54.2%, versus 2 of 13, 15.4%, p < 0.05). Twenty-six patients were died of relapsed breast cancer. In overall survival, patients who was negative for BMM showed higher survival rate (p<0.05).
CONCLUSION
BMM was a good predictor for distant metastasis, especially bone metastasis, and for poor prognosis. But no association was found between bone marrow positivity and tumor size, nodal status, stage, histologic parameter and hormonal receptor status.

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Combination Chemotherapy with VP - 16 , Ifosfamide , and Cisplatin ( VIP ) in the Advanced Non - Small Cell Lung Cancer: Yong Seon Cho, Si Young Kim, Jeong Hee Kim, Hwi Joong Yoon, Kyung Sam Cho; J Korean Cancer Assoc. 2000;32(1):86-92.

Abstract PDF: PURPOSE
We conducted a phase II study in previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer to evaluate the response rate and toxicity of the combination chemotherapy regimen of etoposide, ifosfamide and cisplatin. MATERIALS AND METHODS: From September 1993 to December 1996, twenty patients with advanced non-small cell lung cancer (stage IIIB 5 and IV 15) (squamous cell 8, adeno- carcinoma 12), were enrolled in this study. There were 13 (65%) males and 7 (35%) females, and median age of patients were 56 years (range: 34~66). Eighteen patients had performance status (ECOG) 0~1, two patients had performance status 2. Treatment was consisted of cisplatin (20 mg/m2 i.v., day 1~4), VP-16 (etoposide) (75 mg/m2 i.v., day 1~4), ifosfamide (1000 mg/m2 i.v., day 1~4) with mesna. This treatment was repeated every four weeks.
RESULTS
The overall response rate was 25%. Complete response rate was 5% (1/20) and partial response rate was 20% (4/20). The median cycle of response was 4 (2~6) cycles. The median overall survival time was 28 weeks (9~98 weeks). The median time to progression was 10 weeks (3~50 weeks). Toxicities were evaluated by WHO criteria. Toxicity > GradeIII included: leukopenia 1.6%, thrombocytopenia 3.2%, nausea and vomiting 15%, alopecia 30%, stomatitis 10%. These toxicities were tolerable and reversible.
CONCLUSION
VIP regimen was not superior to previous regimens for advanced non-small all lung cancer, and the toxicities were tolerable.

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The Role of Transbronchial Needle Aspiration for Diagnosis of Bronchogenic Carcinoma: Kwan Young Kim, Jae Yong Park, Seung Ick Cha, Ki Su Park, Tae Kyong Kang, Chang Ho Kim, Tae Hoon Jung; J Korean Cancer Assoc. 2000;32(1):93-99.

Abstract PDF: PURPOSE
Transbronchial needle aspiration (TBNA) has been used for the diagnosis and staging of bronchogenic carcinoma through the flexible bronchoscope. The aim of this study was to investigate the diagnostic role of TBNA for bronchogenic carcinoma.
MATERIALS AND METHODS
TBNA was performed in 34 patients with suspected bron- chogenic carcinoma. We analyzed diagnostic rate of TBNA m 28 patients who were ulti- mately diagnosed as bronchogenic carcinoma.
RESULTS
In 12 of 28 patients, TBNA was performed for endobronchial lesions with a type of infiltration, nodular infiltration or compression. The diagnostic rate was 75%. Addition of TBNA to bronchial washing, brush, and biopsy increased the diagnostic rate from 58% to 80%. In 16 patients with peripheral tumor and mediastinal lymphadenopathy, TBNA was performed for mediastinal lymph nodes. The diagnostic rate was 62.5%, and was positively correlated with the size of lymph nodes. There was no significant complications related to TBNA.
CONCLUSION
TBNA was a safe and effective procedure for the diagnosis of bronchogenic carcinoma in selected patients.

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Detection of Human Papillomavirus DNA and p53 , p21 Gene Expression in CIN3 and Uterine Cervical Cancer: Jae Hyung Na, Ho Sun Choi; J Korean Cancer Assoc. 2000;32(1):100-109.

Abstract PDF: PURPOSE
Though the etiology of this cancer has not been elucidated, it has been suggested that certain types of human papillomavirus (HPV) and alteration of the p53 gene are closely associated with uterine cervical cancer. The aim of the study was to investigate the role of high risk HPV, p53 and p21 gene in cervical intraepithelial neoplasia III (CIN3) and invasive squamous cell carcinoma.
MATERIALS AND METHODS
The presence of high-risk HPV DNA (16, 18, 31, 33, 35, 45, 51, 52, 56) were detected from cervical swab in 240 patients by hybrid capture method. Expression of p53 genes were studied in paraffin-embedded specimens by immunohisto- chemical staining and p53, p21 gene alteration by RT-PCR SSCP using fresh cervical tissues.
RESULTS
High risk HPV DNA were detected in 34%, 74.3% and 75.7% in control, CIN3 and invasive squamaus cell carcinoma respectively. In patients with high risk HPV DNA, type 16 were detected of 5.9%, 30.8%, 47.2% respectively. Relative concentration of HPV DNA to control was 16.3+-27.4 in CIN3 and 30.4+-40.8 in invasive squamous cell cancer. Of patients with high risk HPV DNA, p53 expression was found in 42.9% of CIN3 immunohistochemically, while patients with invasive squamous cell carcinoma was de- tected in 50%. In patients without high risk HPV DNA, p53 expression was detected in 17.1% in CIN3, 15.7% in invasive squamous cell carcinoma. But the mutation of p53 and p21 gene by RT-PCR SSCP were not observed in CIN3 and invasive squamous cell carcinoma.
CONCLUSION
These observations suggest that carcinogenesis of invasive squamous cell carcinoma from CIN3 may be concerned with high risk HPV concentration and may be occurred via another pathway without HPV and p53 or p21 mutation.

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Expressions of Cell Cycle Control Genes in Human Uterine Cervical Cancer Cells: Jung Geol Ahn, Tae Seong Lee, Jae We Cho, Won Ki Baek, Seong Il Suh, Min Ho Suh, Jong Wook Park, Soon Do Cha; J Korean Cancer Assoc. 2000;32(1):110-119.

Abstract PDF: PURPOSE
Recently, many aspects of biological functions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors and Rb gene have been reported, and the cell cycle control genes are considered to act important roles in tumorigenesis. In this study, the expression patterns of major cell cycle control genes (cyclin A, B, C, Dl, E, E2F, p16INK4a, p21WAF1 and Rb) in various human cervical cancer cells were analysed to elucidate the impacts of the cell cycle control genes on the carcinogenesis of human cervical cancer.
MATERIALS AND METHODS
The expression patterns of major cell cycle control genes in HT-3, C33-A, HeLa, C4-II, SiHa and CaSki human uterine cervical cancer cells were analysed by using western blot and reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
In most of the cervical cancer cells tested, the overexpressions of cyclin A, E, E2F and markedly decreased expression of Rb tumor suppressor proteins were observed. By comparing RNA and protein expressions in each cancer cells, the mechanisms of increased expressions of cyclin A, E and decreased expression of Rb were elucidated as post-translational controls.
CONCLUSION
The cervical carcinogenesis caused by the altered expressions of the major cell cycle control genes can be hypothesized as follows: overexpressions of cyclin E and A cause acceleration of Rb phosphorylations and E2F overexpression; increased E2F function accelerates G1/S transition of the cells; compensatory increase of p16 expression cannot stop the cells in Gl phase because Rb expression is severely decreased; consequently, loss of Rb function, 61 shortening, inappropriate cell division and decreased function of the maintenance of genomic stability occur. In addition to these alterations, loss of p53 functions further accelerate instability of genome and decrease the sus- ceptability to cell death. Furthermore, overexpression of Bc12 protects these abnormal cells from apoptosis. All these derangements of cell cycle control should contribute to the human cervical carcinogenesis.

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Chromosomal Aberrations in Ovarian Carcinoma Cell Line, SNU - S , Using Chromosome Painting: Jae Seong Kang, Dae Woon Kim, Yong Hyuck Chun, Sun Hwa Park; J Korean Cancer Assoc. 2000;32(1):120-128.

Abstract PDF: PURPOSE
The characterization of all recognizable chromosomal rearrangements was dis- turbed by technical limitation of conventional cytogenetic methods. Recently, the strong usefullness of generation of chromosome specific painting probes in identification of marker chromosomes has proven. This study was intended to analyze the chromosomal aberrations in human ovarian cancer cell line, SNU-8, by G-banding and multiple paintings.
MATERIALS AND METHODS
Human ovarian cancer cell line, SNU-8 was cultured and harvested for cytogenetic analysis. Routine karyotyping was performed. For complete analysis of chromosomal aberrations, human chromosome-specific painting probes were constructed from somatic hybrid cells. The origins of the unidentified marker chromosomes were analyzed by fluorescent in situ hybridization (FISH) with these painting probes.
RESULTS
All chromosome alterations were confirmed by the use of multiple chromosome paintings, which also demonstrated a number of additional alterations. SNU-8 had the karyotype 62-69,XXX, + der(1;10)(q10;p10),der(3;18) (q10;p10)X2,-4,+ 5,+ 7,del(9)(q21)X2,-11,-13,-15,-16,der(17;19)(q10;q10) X2, + 20,-22[cp51].
CONCLUSION
The chromosomal aberrations of SNU-8 cell line was effectively analyzed by FISH with these painting probes, and the approach methods of this study can be applied to cytogenetic analysis of chromosomal aberrations in the other cancers.

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Relationship of HPV Detection and p53 Expression in Urinary Bladder Cancer: Keun Hong Kee, Hyang Mee Shin, Young Chul Kim; J Korean Cancer Assoc. 2000;32(1):129-135.

Abstract PDF: PURPOSE
The purpose of this study was to investigate the relationship between aberrant p53 expression and the presence of human papillomavirus DNA in transitional cell carcinomas of the urinary bladder.
MATERIALS AND METHODS
This study analyzed 30 paraffin-embedded transitional cell carcinoma of the urinary bladder, including 10 cases of grade I, 10 cases of grade II, and 10 cases of grade III, for the presence of DNA-HPV and abnormal accumulation of p53. We used immunohistochemical staining for p53 protein and in situ hybridization for HPV DNA, respectively.
RESULTS
Overall positive rate of HPV DNA type 16 and type 18 was 60.0% and 53.3%, respectively. Nuclear accumulation of p53 was found in 13 cases (43.3%) of all transitional cell carcinomas. In HPV DNA type 16 positive cases, the p53 was positive in 8 cases and negative in 10 cases. In HPV DNA type 16 negative cases, the p53 was positive in 5 cases and negative in 7 cases. In HPV DNA type 18 positive cases, the p53 was positive in 7 cases and negative in 9 cases. In HPV DNA type 16 negative cases, the p53 was positive in 6 cases and negative in 8 cases.
CONCLUSION
This results suggest that HPV infection and p53 gene accumulation may contribute to the significant role in the carcinogenesis of the utinary bladder. In additon, HPV infection and p53 accumulation may be related to tumor progression and higher grade.

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Expression of Prostatic Carcinoma Oncogene PTI - 1 in Prostatic Carcinoma , Prostatic Intraepithelial Neoplasia and Benign Prostatic Hyperplasia Using in situ PCR: Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; J Korean Cancer Assoc. 2000;32(1):136-147.

Abstract PDF: PURPOSE
Prostatic tumor induced gene-1 (PTI-1) is a mutated human EF-la and putative prostatic carcinoma tumor-inducing oncogene, that is differently expressed in prostatic cancer and benign prostatic hyperplasia. And, it is more sensitive marker than prostate- specific antigen (PSA) for detecting human prostate cancer in the bloodstream. This study invastigated the expression of PTI-1 in paraffin embedded tissue of prostatic carcinoma, prostatic intraepithelial neoplasia, and benign prostatic hyperplasia using in situ PCR.
MATERIALS AND METHODS
we evaluated expression of PTI-1 in prostatic carcinoma with prostatic intraepithelial neoplasia (PIN) of 32 cases, benign hyperplasia of 20 cases, high grade transitional cell carcinoma of 10 cases and colon cancer of 10 cases for control group. Also, the immunohistochemical staining for PSA was performed to comparison with clinical value of PSA.
RESULTS
The serum level of PSA was closely related to stage and Gleason score (p < 0.05). However, the results of immunohistochemical stains were variable to stage and Gleason score. PTI-1 using in situ PCR expressed in 50% of prostatic carcinoma, 41% of prostatic intraepithelial neoplasia, 10% of benign hyperplasia and colon cancer (p < 0.05). No expression is observed in transitional cell carcinoma. In prostatic carcinoma, PTI-1 expressed in 43.8% (7/16) of stage II, 50.0% (5/10) of stage III, and 66.7% (4/6) of stage IV (p<0.05). In PIN, expression of PTI-1 was similar to prostatic carcinoma (p<0.05).
CONCLUSION
PTI-1 represented a relatively sensitive marker for prostatic carcinoma and PIN, indicator of prostatic carcinoma progression.

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Stereotactic Radiotherapy for the Treatment of Brain Metastases: Dae Yong Kim, Yong Chan Ahn, Seung Jae Huh, Jung Il Lee, Do Hyun Nam, Seung Chyul Hong, Hyung Jin Shin, Kwan Park, Jong Hyun Kim; J Korean Cancer Assoc. 2000;32(1):148-155.

Abstract PDF: PURPOSE
To evaluate the clinical results of stereotactic radiosurgery (SRS) and frac- tionated stereotactic radiotherapy (FSRT) for metastatic brain tumors.
MATERIALS AND METHODS
Nineteen patients with brain metastases (34 lesions) were treated with LINAC-based SRS or FSRT with or without whole brain radiotherapy between October 1995 and February 1998. SRS was preferred to FSRT in cases with three or more lesions and poor performance status. FSRT was preferred to SRS in cases with lesions larger than 3 cm and lesions located near or at the eloquent areas such as thalamus, brain stem, and optic apparatus. Single isocenter was used both in SRS and FSRT, and the median peripheral dose in SRS was 15 Gy (range 13~20 Gy), while that in FSRT was 21 Gy (range 15~24 Gy) by 3 Gy per fraction.
RESULTS
Local control was achieved in 79% (27/34 treated lesions) and 1-year over- all survival rate was 58% with the median survival of 12 months. Lethal progressive brain metastases, both local and regional, were in four patients (27% of all deaths). No significant differences in local control and survival was observed with histology, age, sex, performance status, tumor volume, number of lesions, or treatment modality. Unacceptable acute or late complications did not occur.
CONCLUSION
Stereotactic radiotherapy including SRS and FSRT is effective, non-invasive therapy for brain metastases. This study suggests that stereotactic radiotherapy might be an alternative to surgical resection in selected patients of brain metastases.

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Radiation-induced Apoptotic Signaling Pathway in HL - 60 Cells: Sung Ja Ahn, Rae Kil Park, Sang Rock Lee, Woong Ki Chung, Byung Sik Nah, Taek Keun Nam, Hun Taeg Chung, Sun Rock Moon, Heoung Keun Kang, Seung Jin Park; J Korean Cancer Assoc. 2000;32(1):156-167.

Abstract PDF: PURPOSE
The mechanical insights of death of cancer cells by ionizing radiation are not yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study was designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cystein proteases, mitogen-activated protein (MAP) kinases, and transcriptional activation factors in target cells eventually leading to death.
MATERIALS AND METHODS
HL-60 cell line in the log phase was used in this study and the culture media was RPMI 1640. The irradiation was done using the linear accelarator and the radiation does was 10 Gy, 20 Gy, and 30 Gy, respectively. The cell viability was tested by MTT assay and apoptosis was identified by the DNA fragmentation assay. JNK1 (cJun N-terminal kinase) and ERK (extracellular-signal regulated protein kinase) activity was analyzed by the in vitro Ig complex kinase assay. NF- kB (Nuclear Factor- kB) and AP-1 (activator protein-1) activity was assayed by the electrophoretic mobility sbift assay.
RESULTS
Ionizing radiation decreased the viability of HL-60 cells in a time and dose dependent manner. Ionizing radiation-induced cell death of HL-60 cells may be an apo- ptotic death which was evidenced as apoptotic characteristic ladder pattern fragmentation of DNA over 20 Gy at 4 hours. Ionizing radiation specifically induced the activation of CPP32-like cystein protease rather than ICE-like protease of HL-60 cells in a time and dose dependent manner. The activation of CPP32-like cystein protease was also evidenced by the digestion of poly (ADP-ribose) polymerase with 30 Gy ionizing irradiation at 2 hours. The activity of JNK1 was transiently increased up to 3.6 fold by 30 Gy ionizing radiation at 2 hours. Ionizing radiation also rapidly activated the transcriptional activation factors including AP-1 and NF- kB at 10 or 30 min.
CONCLUSION
These data suggested that ionizing radiation-induced apoptosis was mediated by the activation of CPP32-like cystein protease, JNK1, and transcriptional activation factors

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Results of Treatment with ProMACE - CytaBOM Regimen for Aggressive Non - Hodgkins Lymphoma: Wan Kyu Eo; J Korean Cancer Assoc. 2000;32(1):168-177.

Abstract PDF: PURPOSE
Despite intensive search for the optimal combination chemotherapy for aggres- sive non-Hodgkins lymphoma (NHL), the CHOP regimen is still the standard therapy. We investigated the clinical efficacy of ProMACE-CytaBOM, a third generation regimen, in patients with advanced aggressive NHL.
MATERIALS AND METHODS
We prospectively analyzed the therapeutic approach and the outcome in 33 patients with previously untreated aggressive NHL enrolled into the protocol from June 1994 to June 1997.
RESULTS
Objective response was achieved in 93.9% of the patients. Complete response (CR) and partial response were 54.5% and 39.4%, respectively. The mean time to CR was 75.4 days. CR rate was significantly lower in patients aged 50 years or more (31.3% vs 76.5%, p=0.009). Five year overall (OS) and failure-free survival (FFS) rate were 56.1% and 47.2%, respectively. The age, attainment of CR, and mean relative dose intensity influenced OS significantly (p=0.002, p=0.005 and p=0.039, respectively). The age and attainment of CR influenced FFS significantly (p=0.001 and p=0.003, respec- tively). In patients aged 50 or more, mean relative dose intensity of less than 72% was more frequent than younger age group (73.3% vs 33.3%, p=0.003). There was one toxic death (3.0%).
CONCLUSION
The survival rate of present study was similar to that of previously report concerning ProMACE-CytaBOM. The outcome of elderly NHL patients was poor, and dose intensity may be correlated with the outcome.

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A Clinical Study of Pediatric Myelodysplastic Syndrome: Application of International Prognostic Scoring System and the Review of the Korean Literature: Hoon Kook, Chan Jong Kim, Weon Sang Yoon, Na Eun Ryu, Kyoung Joong Chung, Tai Ju Hwang; J Korean Cancer Assoc. 2000;32(1):178-190.

Abstract PDF: PURPOSE
Myelodysplastic syndrome (MDS) in children needs to be elucidated in terms of clinical characteristics, natural history, the most effective treatment and prognostic factors, as the disease is very rare and its definition and classification has not reached a consensus by many physician. This study was aimed to describe the characteristics and the disease courses of Korean children with MDS, and to analyze the usefulness of prognostic scoring systems in the prediction of transformation to acute myelogenous leukemia (AML) and overall survival among subgroups.
MATERIALS AND METHODS
Fourteen children with MDS seen at Chonnam University Hospital and additional 59 patients identified by the review of Korean literature were evaluated to define clinical characteristics and disease courses. Kaplan-Meier (K-M) probability of leukemic transformation and overall survival were plotted. FAB subtypes, subgroups by Boumemouth Scoring System (BSS), and International Prognostic Scoring System (IPSS) risk groups were compared to predict transformation to AML and overall survival.
RESULTS
The median age of 14 patients was 36.5 months. The sex ratio was 3.7:1 (M: F). The frequency of FAB subtypes in Korea was similar to that of other countries except for higher proportion of RA (37%). K-M 3-yr probability of AML transformation and survival for Korean patients were 54.7%, and 49.8%, respectively. Although FAB system, BMS and IPSS were all capable of discriminating subgroups in the prediction of AML transformation and survival, they did not reach the significant level possibly due to small number of patients assigned to each subgroup.
CONCLUSION
The clinical characteristics of Korean children with MDS were not different from those of other countries. This study showed the high rate of AML transformation and poor survival in children with MDS.

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Construction of MAGE - 3 Expressing Plasmid for Development of DNA Vaccine Encoding MAGE - 3 Cancer Antigen: Jong Wook Park, Mi Hyun Lee, Soo Jung Yoon, Won Ki Baek, Seong Il Suh, Min Ho Suh, Kang Dae Lee, Tae Hyun Yu; J Korean Cancer Assoc. 2000;32(1):191-199.

Abstract PDF: PURPOSE
The spectrum of melanoma antigen gene (MAGE)-expressing tumor is very wide and the gene of MAGE express antigens that are targets for specific recognition by cytotoxic T lymphocytes derived from tumor-bearing patients. All of these characteristics represent MAGE as tumor vaccine can be useful for cancer prevention or treatment. Here, we detected MAGE-3 gene expression in cancer cell lines and evaluated recombinant MAGE-3 protein producibility of MAGE plasmid to develope MAGE DNA vaccine.
MATERIALS AND METHODS
MAGE-3 gene expression of cancer cell lines was evaluated by reverse transcription-polymerase chanin reaction (RT-PCR). Two kinds of MAGE-3 expressing plasmids were constructed and their MAGE-3 protein producibility was evaluated by immunohistochemistry and immunoblotting using monoclonal anti-MAGE-3 antibody.
RESULTS
Among 13 cell lines, SNU484, AMC-HN-3, AMC-HN-4, AMC-HN-7, HeLa, NCI H1703 and HT29 expressed MAGE-3 mRNA. In order to make MAGE plasmid, cDNA that showed 100% DNA homology with MAGE-3 gene was cloned into pcDNA 3 plasmid and pSecTag plasmid. Intracytoplasmic and secretory recombinant MAGE-3 was produced by MAGE-3 containing pcDNA 3 plasmid and pSecTag plasmid, respectively.
CONCLUSION
In this study, we showed high expression frequency of MAGE-3 in cancer cell line, and established two kinds of plasmid that produce recombinant MAGE-3 in cell lines. We expect these plasmids will be used in cancer treatment or MAGE-3 function study in future.

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Tumor - specific Virus Replication and Cytotoxicity of E1B 55 kD - deleted Adenovirus: Jaesung Kim, Boyoung Lee, Jinahn Kim, Joong Bae Ahn, Joon Oh Park, Nae Chun Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Heuiran Lee; J Korean Cancer Assoc. 2000;32(1):200-209.

Abstract PDF: PURPOSE
To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo.
MATERIALS AND METHODS
YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l.
RESULTS
PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1.
CONCLUSION
The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.

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Accuraey of Cancer Death Certificates in KOREA: A comparison between diagnoses in the central cancer registry and certified underlying causes of death: Duk Hee Lee, Hai Rim Shin, Don Hee Ahn, Byung Yeol Chun, Sin Kam, Yoon Ok Ahn; J Korean Cancer Assoc. 2000;32(1):210-219.

Abstract: PURPOSE
We evaluated the accuracy of death certificates for persons who registered in the Central Cancer Registry in 1993 and died from 1993 to 1995.
MATERIALS AND METHODS
The study consisted of 27,058 cases which were classified into five groups. according to the possibility of accuracy of the underlying causes of death. We compared the distribution of five groups according to several demographic factors. Also we calculated the detection rate and the confirmation rate for a selected 23,858 persons reported to die of a cancer.
RESULTS
Among the 27,058 deaths, only 64.4% was included in the group which had reported the same cancer site with registry as underlying cause of death. The accuracy decreased with increasing age and was worse for women and rural residence. And physicians certification was an important factor to improve the accuracy. Cancers of stomach, lung, esophagus and breast were included into the high accuracy group, cancers of the colon, rectum and gallbladder and extrahepatic biliary tract into the low accuracy group. Cancers of the colon, pancreas, liver and lung were overreported, varied from 1.2 to 1.4 times, and cervical cancer was severely underreported, about 0.5 times.
CONCLUSION
These results suggest that the caution in the use and interpretation of cancer certificate data would be required.

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Efficacy of Local Radiotherapy as a Salvage Modality for Hepatocellular Carcinoma Which is Refractory to TACE ( Transcatheter Arterial Chemoembolization ): Hee Chul Park, Jinsil Seong, John Jihoon Lim, Gwi Eon Kim, Kwang Hyub Han, Chae Yoon Chon, Young Myoung Moon, Do Yun Lee, Jong Tae Lee, Chang Ok Suh; J Korean Cancer Assoc. 2000;32(1):220-228.

Abstract: PURPOSE
Transcatheter arterial chemoembolization (TACE) has been actively performed for the treatment of unresectable or inoperable hepatocellular carcinoma. However, for the patients with treatment failure after TACE, few options are available for salvage. The purpose of this study was to investigate the efficacy of local radiotherapy as a salvage moda- lity for treatment failure after TACE.
MATERIALS AND METHODS
From January 1993 to December 1997, 27 patients were included in this study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Childs class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Mean tumor size was 7.2+/- 2.9 cm. Liver cirrhosis was associated in 10 patients. Portal vein thrombosis was presented in 5 patients. Serum alpha-fetoprotein was positive in 8 patients. According to VICC staging, the number of patients in III and IVA were 17 and 10, respectively. Treatment failure to TACE was evaluated by CT scan and angiography. Radiotherapy was given to the field including tumor with generous margin using 10-MV X-ray. Mean tumor dose was 51.8+-7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on CT scans 4~6 weeks following completion of treatment.
RESULTS
An objective response was observed in 16 of 24 patients who were possible to be evaluated, giving a response rate of 66.7%. Survival rates after salvage radiotherapy at 1, 2, 3 years were 55.9%, 35.7%, and 21.4%, respectively. The median survival was 14 months. Six patients among responders are surviving at present. Acute toxicity included G1 elevation of AST/ALT in 4 patients, G2 thrombocytopenia in 2, G2 hyperbilirubinemia in 5, and G2 hypoalbuminemia in 3. During follow-up, 4 patients developed ascites. At 6 months after treatment, gastric ulcers and duodenal ulcer were developed in 2 and 1 patient, respectively.
CONCLUSION
Local radiotherapy for treatment failure after TACE in hepatocellular carci- noma appears to be a feasible and effective salvage modality. It gives a 66.7% response rate with a median survival of 14 months. Acute toxicity was self-limiting and manageable. Gastric and duodenal ulcer were significant toxicities after treatment. Further studies are required to find optimal methods of radiotherapy to minimize toxicity.

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Insular Carcinoma: An Aggressive Subtype of Differentiated Thyroid Neoplasms: Seok Jin Nam, Sang Dal Lee, Young Ryun Oh, Jung Hyun Yang; J Korean Cancer Assoc. 2000;32(1):229-234.

Abstract: PURPOSE
Insular carcinoma is a rare subtype of thyroid cancer which is first described by Carcangiu in 1984. It is intermediate in aggressiveness between well differentiated and anaplastic thyroid carcinoma. But its origin, clinical features and prognosis are not yet clearly understood. We wanted to evaluate the clinical features, histologic characteristics and the prognosis of the insular thyroid carcinoma.
MATERIALS AND METHODS
We studied 4 cases of insular thyroid carcinoma treated in Samsung Medical Center from March 1996 to April 1998. Age, sex, clinical features, treatment, pathology and follow up findings were reviewed, retrospectively.
RESULTS
All patients were female and mean age was 44 years. Three of four patients complained anterior neck mass and one patient complained low back pain and paresthesia of right thigh. Two patients had metastatic bone lesions at the time of diagnosis. Preoperative fine needle aspiration cytology could diagnose follicular neoplasm in 2 cases and papillary carcinoma in 1. We performed total or completion thyroidectomy and radioactive iodine therapy in 3 cases and radioactive iodine therapy alone in one. Extra- thyroidal invasion, vascular invasion and multicentricity was noted in two cases. All four patients showed recurrence or distant metastasis in follow up period of 10~31 months and 2 of them died of distant metastasis.
CONCLUSION
Insular carcinoma is a special type of thyroid carcinoma with aggressive clinical course. Recurrence and extrathyroidal involvements are common and the prognosis is poorer than other well differentiated thyroid carcinoma.

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