Cancer Research and Treatment

Angiogenesis and Proliferating Cell Nuclear Antigen Index in Non-small Cell Lung Carcinomas: Chang Hoon Lee, Kang Suek Suh; J Korean Cancer Assoc. 1999;31(5):1054-1064.

Abstract PDF: PURPOSE
This study aimed to determine the relationship between angiogenesis and tumor cell proliferation evaluated by proliferating cell nuclear antigen (PCNA) in non-small cell lung carcinomas (NSCLCs) and to investigate the prognostic significance of the factors in them.
MATERIALS AND METHODS
Immunohistochemical staining for factor VIII related antigen, vascular endothelial growth factor (VEGF) and PCNA was performed using paraffin embedded blocks of 57 NSCLC cases. The results were correlated with some clinicopathologic parameters, including age, sex, TNM-T status, TNM-N status, stage, and histologic type.
RESULTS
Microvessel count (MC) was higher in squamous cell carcinoma group than in non-squamous cell carcinoma one (18.4+/-7.3 vs 14.6+/-9.9, p=0.043). PCNA index was higher in lymph node metastasis group than in non-metastasis one (42.1+/-8.9% vs 36.4+/- 14.6%, p=0.043). But the factors were not correlated with other clinicopathologic parameters. The relationship between VEGF expression and MC was significantly recognized (p=0.02), but that between VEGF expression and PCNA index was not. MC was positively correlated with PCNA index (r=0.547, p=0.005).
CONCLUSION
These findings suggest that both MC and PCNA index can be acted as useful indicators of prognosis in NSCLC, but tumor cell proliferation in NSCLC may be more concerned with any growth factor other than VEGF.

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Prognostic Value of PCNA , c-erbB-2 , c-fos in Patients with Non-small Cell Lung Cancer: Yi Hyeong Lee, Joong Bae Ahn, Dong Hwang Shin, Soon Won Hong, Jeong Yeon Shim, Kyung Young Jung, Se Kyu Kim, Joon Chang, Joo Hang Kim, Won Youn Lee, Byung Soo Kim, Sung Kyu Kim; J Korean Cancer Assoc. 1999;31(4):678-685.

Abstract PDF: PURPOSE
Oncogenes, tumor suppressor genes, and growth variables of tumors are important in the assessment of prognosis in lung cancer. The expression of PCNA, c-erbB-2 (HER-2/neu), and c-fos oncoprotein and their prognostic implications in surgically resected patients with non-small cell lung cancer were evaluated.
MATERIALS AND METHODS
Seventy patients with non-small cell lung cancer were included and PCNA, c-erbB-2 and c-fos overexpression were evaluated by immunohistochemical stain using paraffin-embedded tissue.
RESULTS
The mean proportion of PCNA positive cells was 18.6%, and there was no significant difference according to cell type and stage. The median survival time was significantly shorter in the group with high PCNA expression (>10%) as compared with the group with low PCNA expression (<10%) (37 months vs 16 months). Four (6.3%) of 64 cases demonstrated c-erbB-2 positivity. These were all adenocarcinoma cases. c-fos protein was only rarely overexpressed (1/51).
CONCLUSION
PCNA expression was shown to be a useful prognostic parameter in resected non-small cell lung cancer while c-erbB-2 and c-fos oncoprotein were infrequently expressed.

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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.

Abstract 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 Value of p53 and Proliferating Cell Nuclear Antigen ( PCNA ) in Stage 3 Gastric Carcinoma: Hyung Tae Oh, Duk Su Lee, Dong Ho Han, Sang Young Kim, Byung Yi Ahn, Min Chul Kim, Myung Jin Joo, Kwang Min Lee, Woo Young Kim, Sung Hye Sin; J Korean Cancer Assoc. 1998;30(1):31-39.

Abstract PDF: PURPOSE
We evaluated the prognostic significance of p53 and proliferating cell nuclear antigen(PCNA) in stage III gastric carcinoma to determine the correlation between the p53 and PCNA expression and various clinicopathological parameters.
MATERIALS AND METHODS
The expression of p53 and PCNA were studied immunohistochemically in 64 cases of stage III gastric carcinomas with paraffin-embedded tissue specimens which were obtained surgically at the department of surgery, Presbyterian Medical Center from 1991 to 1992. Both expression were compared with known factors of prognosis. Survival rate and other clinicopathological parameters were analysed.
RESULTS
Expression rates of p53 and high PCNA group were 40.6% and 26.6%, respectively. There was no significant correlation between the p53 and PCNA expression and various clinicopathological variables such as age, sex, stage, histology, tumor depth, number of metastatic node, tumor size, site and method of operation. To analyse survival, we evaluated overall survival according to the extent of p53 and PCNA expression. No significant correlations between the p53 and PCNA expression and overall survival were found. CONCLUSION: These results suggest that the p53 and PCNA expression seems to be hard to use as a prognostic indicator in stage III gastric carcinoma.

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Prognostic Significance of Histologic Features, DNA Content, Expression of Proliferating Cell Nuclear Antigen (PCNA), c-fos Protein and Transforming Growth Factor (TGF)-alpha and -beta in Giant Cell Tumor of Bone: Hee Kyung Chang, Sung Hun Yoon, Jae Do Kim, Man Ha Huh; J Korean Cancer Assoc. 1997;29(2):266-279.

Abstract PDF: PURPOSE
This study was attempted to investigate the prevalence of the expression of c-fos protein, TGF-alpha and -beta, PCNA , DNA ploidy pattern and histopathological parameters of giant cell tumor (GCT) of bone and to correlate with prognosis and to extend our understanding on tumorigenesis of GCT.
MATERIALS AND METHODS
Twenty eight cases of paraffin-embedded tissue were studied, classified as recurrent (5 cases) and non-recurrent group (12cases) within the limits of the cases which afforded surgical material on first operation.
RESULTS
No significant difference was observed in cellularity of stromal cells, atypia of stromal and giant cells, presence of hemorrhage and necrosis between recurrent and non-recurrent group. However, presence of more than 10 mitotic figures in 10 high power fields in recurrent group was significantly higher than non-recurrent group (p<0.05). The immunoreactivity for PCNA was seen only in nuclei of stromal cells, whereas nuclei of giant cells showed negative staining. The positivity of PCNA revealed no significant difference between non-recurrent (mean; 40.9%) and recurrent group (34.4%). The expression of c-fos oncogene was seen in 5 cases (100%) in recurrent group, and 8 cases (66.7%) in non-recurrent group, and no significant difference was seen. No significant difference of expression of TGF-alpha was seen in 5 cases (100%) in recurrent group and in 11 cases (91.7%) in non-recurrent group. The expression of TGF-beta in stromal cells was significantly higher in non-recurrent group (80%) compared to recurrent group (100%) (p<0.05). In DNA analysis out of 18 cases, 4 cases (22.2%) were aneuploidy and 14 cases (77.8%) were diploidy. Among 4 aneuploidy cases, 3 cases (75%) had no recurrence, and 1 case (25%) had metastasis to lung and expired. No significant difference of DNA ploidy pattern was seen between the recurrent and non-recurrent group.
CONCLUSION
Presence of more than 10 mitotic figures in 10 high power fields and less expression of TGF-beta are related to higher possibility of recurrence and it is suggested that the number of mitotic figure (more than 10/10HPF) and expression of TGF-beta could be helpful parameters in predicting recurrence of GCT.

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Expression of p53 in the Benign and Malignant Tumor of Prostate: Ki Kwon Kim; J Korean Cancer Assoc. 1994;26(5):793-801.

Abstract PDF: Immunohistochemical expression of the p53 was studied in 20 csses of benign proststic hypertrophy(BPH) and 56 prostatic adenocarcinomas using a monoclonal p53-specific DO7 anti- body (Novocastra, U.K.) on formaline-fixed paraffin-embedded tissue sections. Proliferative activity was determined by immunahistochemical detectian of proliferative cell nuclear antigen (PCNA) using a monoclonal PCIO antibody (Novocastra, U.K.). Eleven of 56 prostatic carcinomas(19.6%) showed strong immunostaining for p53 in more than 20% of tumor cells and 15 (28.6%) had focal(<=20%) immunoreactivity. The glandular epithelium adjacent to carcinomas showed features of prostatic intraepithelial neoplasia which was stained positively for p53 in 25%,but all cases of BPH showed no staining. High grade carcinomas(Gleasons combined score >=7) were associated with more intense and extensive p53 staining. High PCNA staining(higher than 50%)showed more p53 immunoreactivity(81.8%) than those cases with lower PCNA staining(40%). These findings indicste that altered expression of p53 protein occurs in a prostate cancer and is associated with increased proliferative activity and appears to play a role in the develpment of highly malignant prostatic carcinomas.

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Prognostic Significance of Proliferating Cell Nuclear Antigen ( PCNA: Ho Yeong Lim, Joo Hang Kim, Hyun Cheol Chung, Hyo Dong Um, Jin Hyuk Choi, Byung Soo Kim, Dong Hwan Shin, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1995;27(1):18-28.

Abstract PDF: Proliferatina cell nuclear antigen(PCNA) is known to be closely correlated with DNA synthesis and cell proliferation. Proliferative activities of tumors have recently been consid- ered as one of important prognostic factors in a variety of human cancers. A total of 195 gastric carcinomas was evaluated with immunohistochemical study, using an- tibody(PC 10) with special reference to the correlation between PCNA expression and progno- sis. PCNA expression was assessed semi-quantitatively based on the proportion of tumor cells with immunostained nuclei. There was no significant correlation between PCNA expression and clinicopathological variables such as age, sex, tumor site, size, histologic grade, tumor stage, or the presence of lymph node metastases. To analyse survival, we evaluated disease-free survival and overall survival according to the extent of PCNA expression. No significant correlations between PCNA expression and both disease-free survival and overall survival were found. In conclusion, PCNA expression assessed by semi-quantitative PCNA grading system was not a significant prognostic factor in gastric carcinoma.

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Assessment of Cell Proliferation in Primary and Recurrent Colorectal Cancers - Expression of Transforming Growth Factor - α and Prolifer: Jin Sil Seong, Sun Hee Sung, Jung Woon Lee, Hyun Soo Shin, Charn Il Park, Oh Hun Kwon; J Korean Cancer Assoc. 1995;27(2):223-230.

Abstract PDF: Cell proliferation potential has been found to be a significant biological parameter correlated with the clinical outcome. This study was ta investigate the cell proliferation potential in primary and recurrent colorectal tumor tissues. Using paraffin-embedded tissues from the paired primary and recurrent tumors of l0 patients, a simple hematoxylineosin stain was done and immunohistochemical stains for trans- forming growth factor-a(TGF-a) and proliferating cell nuclear antigen(PCNA) were performed through a labeled streptavidine biotin method. DNA contents and S-phase fraction(SPF) of the cells were assessed by flowcytometric DNA analysis. The degree of differentiation was poorer in the recurrent tumors than in primary tumors. In 4 primary tumors with mixed adenocacinoma and mucinous adenocarcinoma, only the mucinous adenocarcinoma companent was shown in the recurrent tumors. There was no difference in TGF-a expression between the primary and the recurrent tumors however, PCNA was overexpressed in the recurrent tumors comparing to the primary tumors. Flow cytometric DNA analysis was successful in 7 paired cases. There was change of the ploidy from the diploidy to the aneuploidy in 4 cases. SPF showed remarkable increase in the recurrent tumors comparing to the primary tumors. These results show high proliferative potential of the recurrent colorectal tumors, which can be measured using PCNA expression and SPF as biomarkers. Based on the results of this study, an effort to establish more refined method to predict recurrence should be pursued.

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Prognostic Significance of c-erbB2 , c-fos , p53 , Proliferating Cell Nuclear Antigen ( PCNA ) and Epidermal Growth Factor ( EGF: Seung Do Lee, Sung Uhn Baek, Chung Han Lee, Bang Hur, Man Ha Huh; J Korean Cancer Assoc. 1995;27(4):527-535.

Abstract PDF: To evaluate the prognostic significance of c-erbB2, c-fos, p53, PCNA and EGF in stage III gastric carcinoma, frequency of their expression was examined by immunohistochemical method in 206 cases of stage III gastric carcinomas with paraffin-embedded tissue specimens which were obtained surgically at the department of surgery, Kosin Medical College from 1984 to 1988. Survival rate and other clinicopathological parameters were analysed. Expression rates of c-erbB2, c-fos, p53, PCNA and EGF were 46.1%, 43.7%, 62.1%, 65.0% and 35.9% respectively. Correlation of expression was found betweer. EGF and c-fos, EGF and c- erbB2, and c-erbB2 and c-fos respectively. c-erbB2 expression was more frequently observed in intestinal type, well or moderately differentiated carcinomas than diffuse type, poorly differentiated or mucinous types(p<0.05). Similarly EGF expression rate was high in intestinal type and low in mucinous or signet ring cell types(p<0.05). Five year survival rates of positive cases and negative cases were 27.4% and 23.9% in c-erbB2, 27.7% and 23.9% in c-fos, 24.0% and 27.8% in p53, 25.1% and 26.4% in PCNA and 20.5% and 28.9% in EGF respectively. There were no significant differences between positive cases and negative cases in survival rates. When the above factors and conventiona1 prognostic fectors such es tumor depth(t3, t4), lymph node invasion(n0, nl, n2), number of positive nodes(l-3, 4-6, 7- ), Laurens types, were en- tered simultaneously into the Cox regression model, number of positive nodes, and RGF expression emerged as independent prognostic factors(p=0.0004, p=0.043 respectively).

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Prognostic Significance of Proliferating Cell Nuclear Antigen ( PCNA ) Expression in Patients with Colorectal Carcinoma: Il Kwon Jung, Hong Jo Choi, Sang Soon Kim, Sook Hee Hong; J Korean Cancer Assoc. 1995;27(4):550-559.

Abstract PDF: Proliferating cell nuclear antigen(PCNA) is an auxiliary protein of DNA polymerase 8 and is considered to correlate with the proliferative state of cells. If such a biologic marker in colorectal cancer tissue correiates with recurrence and poor survival, it would offer a rationale for planning aggressive adjuvant therapy. Authors investigated the prognostic significance of proliferative activity in cancer cells in patients with colorectal carcinoma using PCNA immunohistochemical analysis. An anti-PCNA monoclonal antibody (PC 10) was used to measure proliferation indices in neoplastic colorectal tissues of 61 patients with the different clinical outcomes. The correlations of PCNA labeling index (PCNA LI) with various clinicopathologic factors, recurrence and prognosis were studied. The results obtained were summarized as follows; 1) The PCNA LI become higher as the histologic differentiation decreased and the Dukes stage increased, both of which were statistically significant (p=0.0133 and 0.0001, respectively). 2) The rate of disease recurrence after curative resection (53 cases) was significantly higher in patients with high PCNA LI (PCNA LI>=50) as compared with those with low PCNA LI (PCNA LI<50) (44.4% vs. 14.3%, p= 0.022). 3) In patients with high PCNA LI, prognosis (2-year survival) was significantly poorer than in those with a low index (31.8% vs. 58.6%, p<0.05). As a result of this study, PCNA labeling index as determined by PCNA immuno- histochemical analysis is suggested to be correlated well with the histologic differentiation and tumor stage and to be an effective predictor in colorectal cancer. The PCNA analysis for biologic heterogeneity of patients with colorectal cancer may be useful in the prognostic grouping of patients and planning prophylactic therapy.

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Effects of Retinoic Acid on p53 Protein , Ki - 67 and PCNA / Cyclin Expression in PLC / PRF / 5 Cells: Dae Gon Kim, Cheol Kwon, Wan Hee Yoo, Yee Yup Kim, Deuk Su Ahn; J Korean Cancer Assoc. 1995;27(4):559-570.

Abstract PDF: Retinoic acid(RA), known to have antiproliferative and differentiation-inducing effecte on cancer cells, was examined to evaluate its potential as a chemotherapeutic agent for hepatocellular carcinoma. The treatment of PLC/PRF/5 cells with RA(l0 pM for 8 days)resulted in inhibited growth by 23.8% as compared to that of control. The decreased cell growth rate was started 2 days after RA addition. We examined the level of expressions of the mutated p53 protein, the Ki-67 antigen, and the proliferation cell nuclear antigen(PCNA)in cultured PLC/PRF/5 hepatocelluar carcinoma cells before and after RA treatment. The mutated pM is thought to be involved in oncogenesis of human cancers, and the expressions of the Ki-67 and the PCNA are used to evlauate tumor cell kinetics. The e#xpression of p53 protein was not inhibited significantly in PLC/PRF/5 cells by treatment with 10 M RA in Go/Gi, S, or G/M phase fraction, as detected by immunocytochemical staining using the monoclonal antibody PAb 180 which recognizes both the wild and the mutated p53 protein. Also no significant increase of expression was observed using the monoclonal antibody PAb 240 which binds only the mutated p53 protein. RA treatment increaaed Go unstained fraction from 0.36+-0.06% to 0.7+-0.19% and decreased Ki-67 antigen expresaion significantly from 51.2+0.8% to 46.9+0.4%(p=0.03) in G phase, 14.8 0.5% to 1l.30.5%(p=0.03) in S phase respectively, but increased the fraction of GgM phase from 33.4+-1.1% to 36.8+-1.4%(p=0.02). PCNA expression was also dropped by RA treatment from 50.4+-1.5% to 42.8+-0.3%(p=0.01) in Gw G, fraction, 14.7+-0.5% to 11.9+-0.4%(p=0.02) in S phase, increased G/M phase fraction from 31.3+-l.2% to 42.2+-0.6%(p=0.008). These results suggested that RA may have anticancer effect through the inhibitiion of Ki-67 and PCNA expression in similar cell cycle phase without affecting the expression of mutant p53 protein in PLC/PRF/5 cells was observed. In addition, cell cycle anaysis suggested that RA induced en arrest of G, progression to G, and S phase.

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Thymidine Kinase Activity and Expression of PCNA in Carcinoma of Digestive Organs: Hae Hyeon Suh, Young Jin Kim, Hyun Jong Kim, Shin Kon Kim, Ji Yun Kook, Tai Ju Hwang; J Korean Cancer Assoc. 1995;27(5):738-746.

Abstract PDF: Thymidine kinase(TK) and proliferating cell nuclear antigen(PCNA) are similar in the aspect that both are a part of protein complex group of cellular DNA synthesis and expression period during cell cycle is Gl-S phase. From 30 surgically resected cancers of digestive organs(20 gastric adenocarcinomas and 10 hepatocellular carcinomas), we evaluated TK activity and PCNA labeling index in normal and tumor tissues in order to know the correlation between them and the value as an independent prognostic factor. TK activity of tumor tissue(5.14 nmol/hr/mg) was higher than that of normal tissue(2. 95 nmol/hr/mg). PCNA labeling index of tumor tissue(54.3%) was higher than that of normal tissue(21.4%). According to the originated organ, both gastric and hepatic malignancies revealed higher TK activity and PCNA labeling index than normal tissues. There was a significant correlation between TK activity and PCNA labeling index. In gastric adenocarcinoma, ratio of TK activity between normal and tumor tissue was higher in poorly differentiated group than well or moderately differentiated group. In hepatocellular carcinoma, ratio of TK activity between normal and tumor tissue was higher in the positive capsular invasion group than the nagative. As a conclusion, the TK activity and PCNA labeling index represented the biologic activity of tumor cells and could be used as independent prognostic factors.

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The Assessment of Proliferation cell Uncear Antigen ( PCNA ) in Cervical Carcinoma Patients Infected with Human Papillomavirus types 16 and 18: Soo Nyung Kim, Tchan Kyu Park, Ho Gune Kim, Kyung Sup Kim; J Korean Cancer Assoc. 1995;27(5):773-783.

Abstract PDF: Proliferating cell nuciear antigen (PCNA) is a nuclear protein sssociated with the cell prolif- erative state. The relationship between the presence of human papillomavirus (HPV) and proliferative indices (PI) was studied. Determination of PI was done by immunohistochemical staining via the avidin-biotin-complex immunoperoxidase method and HPV 16 and HPV 18 status by Southern blot hybridization on paraffin-embedded material from 49 patients with carcinoma of the uterine cervix. HPV 16 was present in 15 cases, HPV 18 wes observed in 6 cases, and both HPV 16 and HPV 18 were found in 4 cases. There was significant correlation between PI and HPV types. PI was 59.7+-9.0% in HPV 16 positive lesion, 67.4+-10.6% in HPV 18 positive lesion, 79.4+-4.2% in both HPV 16 and HPV 18 positive lesion, and 57.5+-16.9% in HPV negative lesion. Among cervical adenocarcinomas, PI was 72.5+-5 14.9% in HPV l6 or HPV 18 positive lesion, as compared to 39.8+-15.1% in HPV negative leaion. No correlation was found between HPV-DNA positivity and PI in relation to clinical stages, histologic typea, and lesion size.

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Expression of p53 Protein in Human Gliomas: Yoo Jin Kim, Geong Sin Lee, Hae Jin Jeong, Man Ha Huh; J Korean Cancer Assoc. 1996;28(1):113-122.

Abstract PDF: In an attempt to evaluate expression of p53 and to characterize the role af p53 alterations in pathogenesis and progression of gliomas, 49 tumors were immunostained with monoclonal antibodies against p53, TGF-a, PCNA on archival formalin-fixed, paraffin-embedded materials. The tumors were divided into low-grade(19 cases) and high-grade(30 cases) gliomas. We evaluated whether expression of these proteins are associated with differentiation of the tumor, and analyzed correlations among these proteins. The results are summarized as follows. The overall incidence of p53 expression in 49 gliomas was 49%(24/49). The extent of p53 immunolabelling of tumor ce11s increased from low-grade to high-grade tumors(p=0.002, Chi-Square Score): Low-grade tumors revealed 21 %(4/19) immunoreactivity, whereas, 67%(20/30) reactivity was seen in high-grade ones. A significant correlation between p53 and TGF-a expression was demonstrated(p=0.024). A correlation between expression of p53 and PCNA revealed borderline significance(p=0.064). The results suggest that p53 could be a useful independent prognostic indicator in human gliomas, possibly in combination with TGF-a and PCNA. And also, the results support the hypothesis that p53 mutations play a role in the progression from low-grade to high-grade gliomas.

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Expression of Proliferating Cell Nuclear Antigen and Epidermal Growth Factor Receptor in Colorectal carcinomas : Relation of Clinical and Patho: Young Chae Chu, Joon Mee Kim, Young Sik Kim, Young Bae Kim, Tae Sook Hwang; J Korean Cancer Assoc. 1996;28(3):432-443.

Abstract PDF: To evaluate the prognostic significance of PCNA and EGFR in colorectal carcinoma, the author analysed 66 colorectal carcinomas in paraffin sections immunohistochemically, using the monoclonal antibody PCNA and EGFR and compared with clinicopathological data. The mean PCNA index of colorectal carcinomas was 49.0¡¾10.8%. PCNA index had positive correlation with lymph node metastasis(p<0.001), distant metastasis(p<0.001), modified Dukes' stage(p<0.001), Jass new prognostic classification grouping(p<0.00l), TNM classification(p<0.001) and tumor size over 10.0cm(p<0.05), degree of histologic differentiation(p< 0.01), fibrosis(p<0.05), perineural invasion(p<0.05), lymphatic and vascular invasion(p<0.05). PCNA expression was more pronounced at the infiltrative margins of the tumor and tumor cells within the lymphatic or vascular channels. But there was no relationship between PCNA index and patients age, sex and tumor location, growth pattern, degree of peritumoral lymphocytic infiltration. The positivity of EGFR in colorectal carcinomas was 93.9% and there was an association between staining intensity and the extent of EGFR expression(rs=0.684, p<0.001) and PCNA index(rs=0.451 & 0.432, p<0.001). There was an association between staining intensity and the extent of EGFR expression and modified Duke's stage(p<0.001), Jass grouping(p<0.001), TNM classification(p<0.001), lymph node metastasis(p<0.001), fibrosis(<0.05), lymphocytic infiltration(p<0.05), lymphatics and vascular invasion(p< 0.01). These results suggest PCNA index and EGFR expression may be a useful prognostic factors in colorectal carcinomas. Knowledge af the percentage of PCNA-positive cells could be especially helpful in deciding to treat patients with adjuvant chemotherapy.

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Comparison of PCNA Index between Cancer , Normal Mucosa and Intestinal Metaplasia Around the Gastric Cacner: Jae Bok Lee, Han Kyeum Kim, Seon Hahn Kim, Young Jae Mok, Young Chul Kim, Bum Hwan Koo, Sae Min Kim; J Korean Cancer Assoc. 1996;28(4):639-646.

Abstract PDF: Due to the poor prognosis of advanced gastric cancer, it is well acknowledged that early diagnosis is the most important goal in the approach to gastric cancer. In 1970 Corres et al. reported that a close correlation existed between the occurrence rate of gastric cancer and the prevalence rate of chronic atrophic gastritis or intestinal metaplasia of the gastric mucosa. The purpose of this study is to define the significance of intestinal metaplasia as a precancerous lesion by comparing the proliferative potentials of intestinal metaplasia with that of cancer tissue and normal gastric mucosal tissue. This was accomplished immunohistochemically by measuring and comparing the amount of PCNA protein found in the cancerous tissue, intestinal metaplastic lesions and normal mucosa from the resected samples of gastric cancer patients. We examined resected samples of 86 gastric cancer patients who had been operated on between July 25 and September 23 of 1992, and selected samples of 89 cancerous tissue, 60 intestinal metaplasia tissue and 60 normal mucosa. Each tumor sample was investigated on the histological classification(WHO, Lauren, and Ming classification), degree of mucosal invasion, existence of tumor thrombus and degree of differentiation. PCNA staining was made according to Streptavidin-biotin method. The number of stained cells converted to the percentage of the total number of cells was defined as the PCNA labeling index(LI). Statistical analysis was performed with the Student t-test and ANOVA test by SAS program. Overall, there was no significant difference between the PCNA index of cancer(l6.0%) and intestinal metaplasia(12.6%) with p=0.055, but a significant difference existed between intestinal metaplasia and normal mucosa with an index of 12.6% and 7.42%, respectively(p =0.013). There were na significant differences found between early and advanced cancer(p =0.620). PCNA index was higher with lymph node metastasis than without metastasis in advanced gastric cancer(p=0.009). There were no differences in the LI value in degree of differentiation, tumor thrombi or the Lauren and Ming classifications(p>0.05). PCNA index was higher in the middle and lower zone of the glands of the intestinal metaplasia than normal mucosa. (p=0.001)From the current results, the proliferation potential of peritumoral intestinal metaplasia was found to be higher than normal tissue, and we believe that this lesion should be investigated further as a precancerous lesion. Also, we find the PCNA labeling index to be a useful method as an objective guide for these further investigations.

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