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Original Articles
Role of Loss of O6-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression
Na-Hye Myong
Cancer Res Treat. 2010;42(2):95-100.   Published online June 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.2.95
AbstractAbstract PDFPubReaderePub
Purpose

Functional inactivation of the O6-methylguanine-DNA methyltransferase (MGMT) gene has been demonstrated as loss of MGMT protein and suggested that it plays an important role in primary human neoplasia, including lung cancer. It has also been reported to be associated with the G : C→A : T transition mutation in the p53 gene of lung cancer. The aims of this study were to investigate the role of MGMT expression loss and its prognostic significance in non-small cell lung carcinomas (NSCLCs), and its correlation with p53 overexpression as well as influence on patient survival.

Materials and Methods

112 surgically resected NSCLC specimens were reviewed by medical records for their clinicopathologic variables. Their tissue microarray blocks were immunostained with anti-human MGMT and p53 primary antibodies. Correlation between MGMT loss and the clinicopathologic prognostic factors, including p53 overexpression and the single or combined actions of MGMT loss and p53 overexpression on patient survival were statistically analyzed by SPSS15.0.

Results

Reduced or absent MGMT expression was found in 48 of 112 NSCLCs (43%), and significantly associated with nodal metastasis and squamous or undifferentiated cell types. Loss of MGMT expression was correlated with p53 overexpression in adenocarcinomas, but not in overall NSCLCs. Its solitary or combined actions with p53 overexpression did not have influence on patient survival.

Conclusion

Loss of MGMT expression is a relatively common event in NSCLCs and significantly associated with nodal metastasis and p53 overexpression, suggesting that it may play a major role in pulmonary carcinogenesis, and also in disease progression of NSCLCs.

Citations

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  • O 6 -Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer?
    Birgitta I. Hiddinga, Patrick Pauwels, Annelies Janssens, Jan P. van Meerbeeck
    Lung Cancer.2017; 107: 91.     CrossRef
  • Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX
    Carole Vitellius, Caroline Eymerit-Morin, Dominique Luet, Lionel Fizanne, Fanny Foubert, Sandrine Bertrais, Marie-Christine Rousselet, François-Xavier Caroli-Bosc
    Clinical Drug Investigation.2017; 37(7): 669.     CrossRef
  • Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases
    Xiao-Bing Jiang, Bin Hu, Dong-Sheng He, Zhi-Gang Mao, Xin Wang, Bing-Bing Song, Yong-Hong Zhu, Hai-Jun Wang
    BMC Cancer.2015;[Epub]     CrossRef
  • Bayesian inference supports a location and neighbour-dependent model of DNA methylation propagation at the MGMT gene promoter in lung tumours
    Nicolas Bonello, James Sampson, John Burn, Ian J. Wilson, Gail McGrown, Geoff P. Margison, Mary Thorncroft, Philip Crossbie, Andrew C. Povey, Mauro Santibanez-Koref, Kevin Walters
    Journal of Theoretical Biology.2013; 336: 87.     CrossRef
  • Immunohistochemical Assessment of O6-Methylguanine-DNA Methyltransferase (MGMT) and Its Relationship with p53 Expression in Endometrial Cancers
    Kyung Eun Lee
    Journal of Cancer Prevention.2013; 18(4): 351.     CrossRef
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The Expression of c-myc, bcl-2 and p53 Proteins in Adenocarcinomas of Lung
Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang
Cancer Res Treat. 2004;36(2):146-150.   Published online April 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.2.146
AbstractAbstract PDFPubReaderePub
Purpose

c-myc, bcl-2 and p53 are known to regulate apoptosis. There has been growing interest in analyzing their contribution to the pathogenesis and prognosis in a variety of human cancers. This study was undertaken to investigate the expression of these proteins in pulmonary adenocarcinomas and to determine their relationship with clinicopathologic parameters and survival.

Materials and Methods

Archival tumor tissues from 61 patients with adenocarcinoma of lung were analyzed by immunohistochemistry for the expression of c-myc, bcl-2 and p53 proteins. Clinical information was obtained through the computerized retrospect database from the tumor registry.

Results

Of 61 patients, 32 were men and 29 women with the median age 63 years. 4 had stage I disease, 2 had stage II disease and 55 had stage III disease. The expression of c-myc protein was identified in 13% (8/61) tumors, bcl-2 protein was detected in 1.6% tumors (1/61) and p53 was detected in 77% (47/71) tumors. The association of the expression of c-myc, bcl-2 and p53 was not detected. The survival time was longer in patients expressing c-myc protein than in patients without the c-myc protein expression (p=.045). Neither bcl-2 nor p53 showed the correlation to clinicopathologic variables.

Conclusion

Our data suggest the involvement of p53 alteration in the pathogenesis of lung adenocarcinoma. The c-myc expression in some tumors indicates that c-myc alone may not contribute critically to the development and/or the progression of these tumors. It, however, correlated to the survival time, suggesting the c-myc expression as a favorable prognostic factor possibly through the apoptosis pathway.

Citations

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  • The transcriptional repression activity of STAF65γ is facilitated by promoter tethering and nuclear import of class IIa histone deacetylases
    Feng-Shu Hsieh, Nai-Tzu Chen, Ya-Li Yao, Shi-Yun Wang, Jeremy J.W. Chen, Chien-Chen Lai, Wen-Ming Yang
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.2014; 1839(7): 579.     CrossRef
  • Expression of Matrix Metalloproteinase-9 Correlates with Poor Prognosis in Human Malignant Fibrous Histiocytoma
    Jinyoung Yoo, Ji Han Jung, Seok Jin Kang, Chang Suk Kang
    Cancer Research and Treatment.2004; 36(6): 384.     CrossRef
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Correlation between p53 and Rb Protein Expression and Clinicopathologic Features in Hepatocellular Carcinoma
Mi Jin Gu, Joon Hyuk Choi
Cancer Res Treat. 2003;35(6):514-520.   Published online December 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.6.514
AbstractAbstract PDF
PURPOSE
Hepatocellular carcinomas (HCC) are one of the most common cancers in Korea. The mechanism of HCC development is still unclear, and the aberration of the tumor suppressor genes in HCC remains to be clarified. MATERIALS AND METHODS: To study the expressions of p53 and Rb protein, and their correlation with the clinicopathological parameters in HCC, 68 patients, with surgically resected hepatocellular carcinomas, were analyzed by an immunohistochemical method. The expressions of p53 and Rb protein were classified into three categorizes, depending on the percentage of stained cells. RESULTS: The expression of the p53 protein was 51.5% (35/68), and was significantly correlated with differentiation (p<0.05). The altered Rb protein expression was 72.2% (49/68). The expressions of p53 and altered Rb protein had no significant correlation with the tumor size, gender, WHO histological pattern, cirrhosis or vascular invasion (p>0.05). There was a positive correlation between p53 and Rb protein overexpression (p<0.05). The expressions of p53 and Rb protein had correlation with the Ki-67 labeling index (p<0.05). CONCLUSION: These findings suggest the aberrant expressions of p53 and Rb protein may play a role in the progression and carcinogenesis of HCC.

Citations

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  • Clinical significance of down-regulated HINT2 in hepatocellular carcinoma
    Dong-Kai Zhou, Xiao-Hui Qian, Jun Cheng, Ling-Hui Chen, Wei-Lin Wang
    Medicine.2019; 98(48): e17815.     CrossRef
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Clinical Implications of VEGF and p53 Expression in Squamous Cell Carcinoma of the Cervix Treated with Radiation Therapy
Jin Oh Kang, Seong Eon Hong, Dong Wook Kang
Cancer Res Treat. 2003;35(5):440-444.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.440
AbstractAbstract PDF
PURPOSE
The present study was designed to analyze the relationship between vascular endothelial growth factor (VEGF) and p53, and their impact on clinical outcome in squamous cell carcinoma of the cervix treated with radiation therapy. MATERIALS AND METHODS: This immunohistochemical study involved 23 patients with available paraffin blocks among 46 patients who were treated during the period from 1994 to 1997 in Eulji University Hospital in Korea. Anti-VEGF mouse monoclonal antibody and DO-7 anti- p53 mouse monoclonal antibody were used as the primary antibodies. Antibody binding was detected with a LSAB kit. Staining was defined as positive for VEGF and p53, when more than 10% and 5% of the tumor cells were stained out of 500 cells counted, respectively. RESULTS: FIGO stage (p=0.05) and tumor size (p=0.04) were significant prognostic factors for survival. p53 expression was present in 17 (77%) cases. There was no significant relationship between p53 staining and the clinicopathologic factors, such as FIGO stage (p=0.98), tumor size (p=0.43), lymph node status (p=0.82), parametrial invasion (p=0.96), and age (p=0.18). The five year survival rates according to the p53 expression status were 80% for the p53 negative group and 66% for the p53 positive group (p=0.58). Positive VEGF expression was observed in 11 (47%) of the total of 23 patients. Statistical evaluation of VEGF expression according to stage (p=0.36), tumor size(p=0.11), lymph node status (p=0.82), parametrial invasion (p=0.49), and age (p=0.55) revealed no significant difference in any of these parameters. The five year survival rates according to the VEGF expression status were 89% for the VEGF negative group and 41% for the VEGF positive group (p=0.07). CONCLUSION: We suggest that VEGF expression may have an effect on the prognosis of cervix cancer patients treated with radiation therapy, and further evaluation with a large sample size is warranted.

Citations

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  • Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review
    Huifang Wang, Chang Liu, Keer Jin, Xiang Li, Jiaxin Zheng, Danbo Wang
    Biomedicine & Pharmacotherapy.2024; 180: 117483.     CrossRef
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Clinical Significance of p53, c-erbB-2, Chromogranin A and PCNA in the Ampullary Carcinoma
Ki Hwan Kim, Sun Whe Kim, Woo Ho Kim, Yong Hyun Park
J Korean Cancer Assoc. 2001;33(1):84-91.
AbstractAbstract PDF
PURPOSE
To determine the clinical significance of p53, c-erbB-2, chromogranin A (CgA), proliferating cell nuclear antigen (PCNA) expression in ampullary carcinoma, a retrospective study was performed.
MATERIALS AND METHODS
The cases of 96 patients who underwent curative resection for ampullary carcinoma during the ten-year period (1986-95) were reviewed. And, using paraffin-embedded tumor tissues, immunohistochemical (IHC) staining for p53, c-erbB-2, CgA, and PCNA was performed.
RESULTS
The overall five-year survival rate (5-YSR) for these 96 patients was 58%. With regard to TNM stage, the 5-YSR was 71% for stage I (n=36), 62% for stage II (n=29), and 39% for stage III (n=31), respectively. IHC expression rate was 17.6% for c-erbB-2, 19.2% for CgA, and 42.9% for p53. The relative proportion of labelling index of PCNA (<25%, 25-50%, >50%) was 30.8%, 25.3%, and 44.0%, respectively. The PCNA labelling index showedsignificant correlation with tumor size (p=0.032). The PCNA labelling index, c-erbB-2, CgA and p53 were not correlated to extent of invasion, lymph node metastasis, stage, or histologic type. CgA and c-erbB-2 expression and the PCNA labelling index thus had no prognostic value. With regard to p53, the 5-YSR of p53 negative cases was 68.6%; that of p53 positive cases was 47%, with significant difference (p=0.038).
CONCLUSION
This result suggests that p53 expression is related to poor prognosis of ampullary carcinoma, and that c-erbB-2 and CgA expression, and the PCNA labelling index, are not significant prognostic factors.
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Apoptosis in Renal Cell Carcinoma: Correlation to Apoptosis Related Genes and Cell Proliferation, and Its Prognostic Significance
Ji Shin Lee, Jong Jae Jung, Sung Taek Lee, Chang Soo Park
J Korean Cancer Assoc. 2001;33(1):9-15.
AbstractAbstract PDF
PURPOSE
To investigate the prognostic role of apoptosis and to evaluate the relationship between apoptosis and apoptosis-related genes, as well as cell proliferation in renal cell carcinoma (RCC).
MATERIALS AND METHODS
Apoptosis was detected by using the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) technique in 67 formalin-fixed and paraffin-embedded RCC specimens. Immunohistochemical stainings for p53 and retinoblastoma (Rb) proteins and proliferating cell nuclear antigen (PCNA) were also conducted simultaneously.
RESULTS
The apoptotic index (AI) varied from 0.2% to 25.5%. The PCNA index (PI) ranged from 2.1% to 70.3%. The expression of p53 protein was found in 31 of 67 (46.3%) cases. Abnormal expression of Rb was seen in 23 of 67 (34.3%) cases. There was a statistically significant positive correlation between AI and increasingnuclear grade (p<0.001). A significant correlation was found between AI and PI (r=0.329, p<0.01). When comparing the AI with the expression of p53 and Rb proteins, there was no significant difference. In univariate survival analysis, nuclear grade, TNM stage, PI, expression of Rb and AI were significantly associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis.
CONCLUSION
The present findings indicate that apoptosis in RCC is closely associated with cell proliferation, but not with the expression of p53 and Rb proteins. In multivariate analysis, the AI does not carry an independent prognostic significance.
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Expression of p53, bcl-2 Protein in Small Cell Lung Cancer (SCLC) Cell Lines in Relation to Sensitivity to Chemotherapy
In Sook Woo, Myung Jae Park, Young Seok Park, Sung Won Jung, Mi Ae Yeo, Soo Hyun Park, Si Young Kim, Hwi Joong Yoon, Kyung Sam Cho, Jae Kyung Park, Young Il Kim
J Korean Cancer Assoc. 2000;32(5):904-910.
AbstractAbstract PDF
PURPOSE
Sensitivity of tumor cells to chemotherapeutic regimen may be accentuated by their abnormal expression of oncogene. p53 is required for the efficient activation of apoptosis following irradiation or treatment with chemotherapeutic agents. The aim of this study was to evaluate the relationship between chemosensitivity and apoptosis related proteins such as p53, bcl-2 in small cell lung cancer cell lines. MATERIAL AND METHODS: Six human small cell lung cancer cell lines, NCI-H69, NCI-H128, NCI-H1436, NCI-H1092, derived from untreated and treated patients were tested for chemo sensitivity and the expression of the p53, bcl-2 genes were examined in each cell lines with western blot analysis. We used 4 drugs including adriamycin, cisplatin, vincristine and VP-16.
RESULTS
NCI-H128 was the most sensitive cell line to four drugs. NCI-H82 and NCI-H1092 were highly resistant to VP-16, adriamycin and vincristine and determination of an IC50 was not possible. In western blot analysis, NCI-H128 alone was strong positive to p53 monoclonal antibody and the rest of cell lines were negative. All but NCI-H128 were positive to bcl-2 monoclonal antibody. NCI-H128 which was strong positive to p53 and negative to bcl-2. NCI-H1092 was strong positive to bcl-2 and negative to p53 monoclonal antibody.
CONCLUSION
We were not able to explain the expression of p53 in small cell lung cancer cell lines in relation to senitivity to anti-cancer chemotherapeutic agents. But the expression of bcl-2 in small cell lung cancer cell lines was correlated with the chemosensitivity well.
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Immunohistochemical Expression of p53 and Cathepsin D in Prostatic Carcinoma
Dae Joong Kim, Eui Han Kim, Seung Ha Yang, Chang Jin Kim
J Korean Cancer Assoc. 2000;32(4):810-816.
AbstractAbstract PDF
PURPOSE
To evaluate the prognostic significances of p53 and cathepsin D in the prostatic carcinoma, we compared them to other prognostic factors, such as nuclear grade and clinical stage.
MATERIALS AND METHODS
The material consisted of 40 paraffin-embedded, primary prostate carcinomas. We examined the expression of p53 and cathepsin D using immunohistochemical staining and compared their expression with the grade and stage.
RESULTS
The expressions of p53 were noted in the nucleus of tumor cells and cathepsin D were noted in the cytoplasm of tumor cells. Thirteen of 40 tumors were positive for p53. There were more expressing p53 in samples (40%) from prostatic cancer with a high Gleason score group than in samples (28%) from prostatic cancer with low Gleason score group. The expression of p53 was 22% in clinical stage B and C groups and 35% in clinical stage D group. These results showed that p53 expression was not statistically correlated with Gleason score and clinical stage, but there were trends to increased p53 expression with high Gleason score and progressed clinical stage (p>0.05). Progressed clinical stage group showed higher expression of cathepsin D than early clinical stage group. However, there were no statistical correlations between expression of cathepsin D and Gleason score, and clinical stage (p>0.05).
CONCLUSION
These results suggest that the overexpression of p53 and cathepsin D may be associated with tumor differentiation and clinical stage, but have limited prognostic value in prostatic carcinoma.
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Clinical Significance of Apoptosis and p53 Protein Expression in Stage IIB Squamous Cell Carcinoma of the Cervix Treated with Radiotherapy Alone
Eun Ji Chung, Gwi Eon Kim, Jinsil Seong, Woo Ick Yang, Young Tae Kim, Chang Ok Suh
J Korean Cancer Assoc. 2000;32(3):638-646.
AbstractAbstract PDF
PURPOSE
The purpose was to investigate the spontaneous apoptotic index (SAI) and p53 protein expression and to identify the role of SAI and p53 protein positivity.
MATERIALS AND METHODS
Forty six patients with squamous cell carcinoma of the cervix, FIGO stage IIB, treated with curative radiotherapy alone between 1990 and 1993 were included in this study. Definitive radiotherapy including external beam and high-dose-rate brachytherapy was given. Pretreatment paraffin-embedded biopsy specimens of those patients were scored for apoptosis and p53 protein expression using mouse mondegrees Clonal antibody (DO-7) by immuno staining. Clinicopathologic characteristics were also studied in relation to SAI and p53 protein expression, and as prognostic factors for clinical outcome.
RESULTS
SAI and p53 were not related to any clinical characteristics. The range of the SAI was 0.2~4.7% (median 1.1%, mean 1.5%). The rate of p53 protein expression was 65.2% (30/46). Patients whose tumors had high SAI and low p53 protein positivity had better treatment outcome than those with lower SAI. There was also a significant correlation between the SAI and p53 protein expression.
CONCLUSION
The pretreatment SAI and p53 oncoprotein expression are clinically useful in predicting the clinical outcome of FIGO stage IIB squamous cell carcinoma of the uterine cervix patients treated with definitive radiotherapy.
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The Role of bcl-2 and p53 in Tamoxifen-Induced Apoptosis of Human Breast Cancer Cell Lines
Woo Chul Noh, Dong Young Noh, Yong Ho Ham, Chang Min Kim, Nam Sun Paik, Nan Mo Moon, Kuk Jin Choe
J Korean Cancer Assoc. 2000;32(3):531-538.
AbstractAbstract PDF
PURPOSE
Tamoxifen has been well known as an effective anti-tumor agent against breast cancer. The important role of bcl-2 and p53 proteins in tamoxifen-induced apoptosis of breast cancer cells has been suggested. However, the paradoxical fact that bcl-2 over-expression is assdegrees Ciated with better prognosis in clinic has not yet been clearly explained. To investigate this paradox, we analyzed the effect and dynamics of bcl-2 and p53 on the apoptosis after treatment of breast cancer cells with tamoxifen.
MATERIALS AND METHODS
The human breast cancer cell lines MCF-7 and MB MDA-468 were treated with 17-betaestradiol (E2) and tamoxifen.
RESULTS
Following tamoxifen treatment, MCF-7 cells underwent apoptosis accompanied by reduced bcl-2 expression. E2 pre-treatment led to the inhibition of tamoxifen-mediated apoptosis and bcl-2 down-regulation. When MB MDA-468 cells were treated with E2 or tamoxifen, bcl-2 and p53 protein expression did not change and apoptosis did not develop.
CONCLUSION
We observed that the down-regulation of bcl-2 by tamoxifen treatment can facilitate the apoptosis of breast cancer cells without p53 mutations. This finding was consistent with clinical experiences in which bcl-2 positive tumors were assdegrees Ciated with more indolent phenotypes in breast cancer.
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Expression of MDM-2 and p53 Proteins in Gastric Adendegrees Carcinoma and Its Relationship with Clinicopathologic Factors
Ji Woong Yang, Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyoung Yoo
J Korean Cancer Assoc. 2000;32(3):476-486.
AbstractAbstract PDF
PURPOSE
MDM-2 is an oncoprotein that inhibits p53 tumor-suppressor protein. These abnor malities have a role in tumorigenesis through inactivation of p53 function. To determine the clini copathological and prognostic value of MDM2 abnormalities in gastric adendegrees Carcinoma, MDM-2& p53 protein expression were analysed in surgically resected materials of gastric adendegrees Carcinoma.
MATERIALS AND METHODS
Fifty cases which had got follow-up after surgical resection were immunohistdegrees Chemically studied with p53 and MDM-2 antibodies. We defined variable clinico pathologic factors for expression of p53 and MDM-2 protein and analysed their relationships.
RESULTS
Immunohistdegrees Chemical stain revealed expression of MDM-2 protein as a 52.0% (26/50) and p53 protein 20.0% (10/50), respectively. But their expressions were not assdegrees Ciated with clinicopathological factors such as T-factor, N-factor, stage, histology and differentiation. Overall, p53-negative patients seemed to have a better prognosis regardless of MDM-2 protein status (P= 0.057). MDM-2 protein status was considered to have no play as a prognostic factor.
CONCLUSION
In the gastric adendegrees Carcinoma, p53 protein expression seemed to have a inverse relationship with clinical outcomes but MDM-2 protein expression, which was observed more frequently than those of p53, seemed not to be prognostic indicator.
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Expression of p53, p21/WAF1, bcl-2 and Loss of Heterozygosity for the Study of Apoptosis in Gastric Carcinoma
Hang Jong Yu, Joo Ho Lee, Woo Ho Kim, Kuk Jin Choe, Jin Pok Kim
J Korean Cancer Assoc. 2000;32(3):447-457.
AbstractAbstract PDF
PURPOSE
The purpose of this study was to correlate the immunohistdegrees Chemical expressions of p53, p21 and bcl-2, with their loss of heterozygosity (LOH) and clinical significance.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 30 patients with gastric car cinomas were examined for immunohistdegrees Chemical staining and LOH study. Primary antibodies used in immunohistdegrees Chemical staining were mouse mondegrees Clonal antibody to human p53, p21/ WAF1 and bcl-2. For PCR-LOH assays, D6S271, D6S105, D18S386, TP53, D17S796, and D17S786 microsatellite markers were used.
RESULTS
The expression rates of p53, p21 and bcl-2 were 76.7%, 80% and 3.3%, respectively. The expression of p21 was correlated with lymph node metastasis. LOH were found in 20.8% at D6S271, 42.3% at D6S105, 31.6% at D18S386, 39.1% at TP53, 40.9% at D17S796, and 50.0% at D17S786. No correlation was found between the immunohistdegrees Chemical expression and the LOH in these gene sites.
CONCLUSION
p53 and p21 were detected in high rate, whereas bcl-2 expression rate was very low in gastric adendegrees Carcinoma. Of them, overexpression of p21 was correlated with the tumor progression. High incidence rate of LOH may play an important role in gastric carcinogenesis. These findings suggest that the effects on apoptosis and cell cycle by p53 and p21 were important in development and progression of gastric cancer.
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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.
AbstractAbstract 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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Type of Intestinal Metaplasia in the Surrounding Mucosa of Gastric Carcinoma and Expression of bcl-2, p53 and c-erbB-2 Prtein in Gastric Carcinoma
Seung Che Cho, Kun Young Kwon
J Korean Cancer Assoc. 1999;31(5):898-911.
AbstractAbstract PDF
PURPOSE
This study was carried out to clarify significance of types of intestinal metaplasia and roles of bcl-2, p53 and c-erbB-2 protein in the development of gastric carcinoma.
MATERIALS AND METHODS
Total one hundred fifty nine cases of surgically resected stomachs with benign ulcer (n=21), dysplasia (n=18) and gastric carcinoma (n=120) were studied histologically, histochemically and immunohistochemically.
RESULTS
Type III intestinal metaplasia was significantly more common in the carcinoma patients in older age group. Bcl-2 expression was found in 94.4% cases of dysplasia and 75.0% cases of carcinoma. Positivity for bcl-2 protein was significantly higher in intestinal type carcinomas than in diffuse type carcinomas (p=0.000). The expression of p53 protein showed 50.0% cases of dysplasia and 49.2% cases of carcinoma. The expression of p53 protein was significantly correlated with depth of invasion (p=0.000), regional lymph node metastasis (p=0.001), and tumor size (p=0.001). C-erbB-2 protein was only expressed in 15.0% cases of carcinoma. The expression of c-erbB-2 protein was found more often in advanced carcinomas (p=0.001) and carcinomas with regional lymph node metastasis (p=0.003).
CONCLUSION
Type III intestinal metaplasia was associated with age, but not with types of gastric carcinoma. Bcl-2 protein is probably involved in dysplastic lesion of gastric carcinogenic sequence and associated with intestinal type carcinoma, and p53 protein is also involved in dysplasia. p53 protein and c-erbB-2 protein may have a role of tumor invasion and nodal metastasis as poor prognostic factors.
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Expression of p53 Protein and Proliferating Cell Nuclear Antigen in Epstein - Barr Virus-associated Gastric Adenocarcinoma
Jeong Hee Kang, Chang Hoon Lee, Kang Suek Suh
J Korean Cancer Assoc. 1999;31(3):429-440.
AbstractAbstract PDF
PURPOSE
Recently, it has been reported that Epstein-Barr virus (EBV) is associated with some gastric cancers. But EBVs role in EBV-associated gastric carcinomas (EBVaGCs) has not been fully elucidated. This study was undertaken to evaluate the characteristics of EBVaGCs and to compare those with non-EBVaGCs.
MATERIALS AND METHODS
EBV infection was studied using paraffin-embedded tissue blocks of 119 cases of gastric adenocarcinomas by in situ hybridization for EBV-encoded small RNAs (EBERs). In EBVaGCs and non-EBVaGCs, molecular characteristics were evaluated by immunohistochemical staining for latent membrane protein (LMP)-1, p53 protein, and proliferating cell nuclear antigen (PCNA).
RESULTS
EBERs were detected in 12 cases (10.1%) of 119 gastric adenocarcinomas. LMP-1 was negative in all carcinomas tested, p53 protein was positive in 7 cases (58.3%) of 12 EBVaGCs and in 51 (47.7%) of 107 non-EBVaGCs, the difference between two groups being not significant. Mean PCNA index was 38.2+-26.1% in EBVaGCs and 22.8 +- 20.0% in non-EBVaGCs. The index was significantly higher in the former than in the latter.
CONCLUSION
These results suggested that neoplastic progression in EBVaGCs was implicated with high expression of PCNA, but not consistently with overexpression of p53 protein or LMP-1.
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Prognostic Significances of p53 Protein and Other Prognostic Factors in Hepatocellular Carcinoma Patients
Gui Tark Hong, Dong Wook Choi, Jong Inn Lee, Nam Sun Paik, Nan Mo Moon, Seung Sook Lee
J Korean Cancer Assoc. 1995;27(6):916-924.
AbstractAbstract PDF
Hepatocellular carcinoma(HCC) is the one of most frequent cancers in Korea,and the mortality rate from HCC is highest in this country all over the world, probably due to high hepatitis B virus infection rate and extremely poor progonosis. Established prognostic factors in HCC are presence of venous invasion, multiplicity and curative resection, but we do not know all about prognosis in curatively resected cases. So, we studied p53 protein expression in Korean HCC patients, which is independent prognostic factor in breast cancer and lung cancer. We performed immunohistochemistry using Pab 180l, which is monoclonal antibody for p53 protein in 39 HCC patients, who underwent curative liver resection in Korea Cancer Center Hospital. Positive expression rate of p53 protein was 26 %. The p53 protein expression seemed to be higher in HCC patients with poor prognostic factors such as vein invasion, absence of encapsulation, and multiplicity, but they did not reach the stastistical significance. And slightly better survival rates were shown in p53 negative protein group, but no significant difference was detected(p=0.593). In conclusion, we could not detect the prognostic significance of p53 protein expression in curatively resected HCC patients, but we think that more extensive study will be needed in more patients using diverse antibodies to mutant p53 protein.
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The Expression of the Mutant p53 Protein in Colorectal Tumors
Seung Ik Jang, Chang Soo Kim, Jong Chan Lee, Suk Kyun Chang
J Korean Cancer Assoc. 1996;28(2):215-225.
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It is known that the development of colorectal tumor needs several sequential abnormality of chromosome in 5p, I8q and 17p and chromosomal abnormality in 17p especially causes malignant transformation of colorectal tumor. The mutation of p53 gene in chromosome 17p proceed the loss of that. Abnormal nuclear protein known as mutant p53 protein is expressed in the early phase of malignant transformation of colorectal tumor. We examined the mutant p53 protein in 115 paraffin-embedded colorectal tumors and normal tissues(group 1: 15 normal tissues, group 2; 30 adenomas and group 3; 70 adenocarcinoma) by immunohistochemical method using monoclonal antibody to the mutant p53 protein. The degree of positive expression of the mutant p53 protein in each group was graded and it was compared in accordance with several prognostic factors of colorectal cancer. In normal tissues and adenomas, positive expression of the mutant p53 protein was not found. In adenocarcinoma, the mutant p53 protein was positively expressed with gradual decreasing tendency from 50.0% of Dukes' A, 48.0% of Dukes' B, 40.9% of Dukes' C to 26.7 % of Dukes' D. The positivity of Dukes' A, B, and C was significantly different from that of Dukes' D.(p<0.05). The mutant p53 protein in adenocarcinoma without lymph nodes involvement, lymphatic invasion, perineural invasion and vein invasion was positively expressed as 48.5%, 47.8%, 50.0% and 44.1%, respectively. That was expressed higher than 39.4% , 38.3%, 20.0% and 27.3% in same group with positive pathologic findings(p<0.05, *p<0.01). The mutant p53 protein in adenocarcinomas of rectum and ascending colon was positively expressed by 48.7% and 40.0%. That was expressed higher than 33.3% and 22.2% in same group of sigmoid colon and transverse and descending colon. The mutant p53 protein was positiveiy expressed in well and morderately differentiated adenocarcinoma as 45.5% and 45.3%. None of poorly differentiated adenocarcinomas and mucinous carcinomas positively expressed, From the above experiment, we found that the mutant p53 protein was exclusively expressed in adenocarcinoma and that positive expression rate was reversely correlated to the clinical staging and severity of invasiveness. In conclusion, we thought that the expression of the mutant p53 protein might have a prognostic value in the colorectal cancer.
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Cancer Res Treat : Cancer Research and Treatment
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