Journal of Pathology and Translational Medicine

Original Articles

Correlation between Nuclear Grades and the Numbers of AgNORs and PCNA Labeling Indices in Renal Cell Carcinoma.: Hye Jin Lee, Young Im Han, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1996;30(2):132-139.

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Abstract PDF: The author examined the number of AgNORs and PCNA labeling indices by histochemical and immunohistochemical studies in 20 cases of renal cell carcinoma, composed of 5 cases according to the nuclear grades. The results obtained are summarized as follows; 1) Mean number of AgNORs according to the nuclear grades of renal cell carcinoma were 1.38+/-0.40 (mean+/-standard deviation) for Grade I, 2.53+/-0.33 for Grade II, 5.43+/-0.66 for Grade III, and 7.88+/-0.72 for Grade IV. The mean numbers of AgNORs according to the nuclear grades were significantly increased(p=0.0005). 2) PCNA labeling indices (positive nuclear ratio) according to the nuclear grades of renal cell carcinoma were 5.90+/-2.36 for Grade I, 19.30+/-6.71 for Grade II, 45.73+/-8.62 for Grade III, and 61.83+/-6.34 for Grade IV. Also, the PCNA labeling indices according to the nuclear grades were significantly increased(p=0.0008). 3) The mean numbers of AgNORs directly correlated with the PCNA labeling indices (r=0.9861, p<0.001). On the basis of the above results, it was considered that the numbers of AgNORs and PCNA labeling indices as markers of proliferative activity of tumor cells correlate well with the nuclear grades of renal cell carcinoma.

Evaluation of Prognostic Significance of AgNORs and PCNA during 9,10-dimethyl-1,2-benzantracene(DMBA)-induced Hamster Buccal Pouch Carcinogenesis.: Sam Pyo Hong, Myong Soon Song, Seong Doo Hong, Jae Il Lee, Chang Yun Lim; Korean J Pathol. 1998;32(5):337-345.

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Abstract: The purpose of this study is to evaluate the prognostic significance of argyrophilic nucleoalr organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) by using DMBA hamster buccal pouch carcinogenesis which provides a good experimental model in reproducing steps from precancerous lesions to invasive squamous cell carcinomas. The buccal pouches of 50 Syrian hamsters were applied with 0.5% DMBA in mineral oil three times a week to reproduce various lesions from precancerous ones such as hyperkeratosis or epithelial dysplasia to invasive squamous cell carcinomas. Their sections were stained with H & E, and silver colloid, and processed immunohistochemically by being applied with monoclonal antibody to PCNA. The histopathologic examainations were done and the counts of AgNORs were evaluated. The PCNA labelling indices on each lesions were evaluated. The correlation between histopathological grades and counts of AgNORs or PCNA labelling indices were evaluated. The number of AgNORs was 2.22+/-0.22 in control group, 3.46+/-0.72 in carcinoma in situ (CIS), 3.78+/-0.63 in squamous cell carcinoma (SCC), respectively. AgNORs significantly increased in severe epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The PCNA Labeling Index (LI) was 39.47+/-6.68% in control group, 79.61+/-4.14% in CIS, and 85.43+/-6.25% in SCC, respectively. PCNA LI also significantly increased in epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The number of AgNORs, AgNOR area, and PCNA LI slightly increased in the advancing front than in the center of SCC, but, it was not statistically significant. It appeared that there were a good correlation between the number of AgNORs and PCNA LI (Pierson correlation coefficient : 0.649, P<0.001). These results suggested that the number of AgNORs and the PCNA LI could be useful markers for evaluating the risk of malignant transformation and prognosis of SCC. It was thought that the clinical usefulness of these markers should be verified by using human tissue specimens.

Prognostic Significance of PCNA Index and AgNORs Score in Transitional Cell Carcinoma of the Renal Pelvis.: Wan Seop Kim, Seung Sam Paik, Nam Hoon Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(7):521-530.

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Abstract: Proliferative activity of a malignant tumor is known to reflect its biological aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells. In transitional cell carcinoma of the renal pelvis, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNORs count in 22 transitional cell carcinoma of the renal pelvis to assess their prognostic significance compared with their cumulative survival rate, the stage of disease and histopathologic features of the tumors. An immunohistochemical method and a standard colloidal silver staining were used. The mean percentage of PCNA positivity (PCNA index) and the mean number of AgNORs per nucleus (AgNORs score) were determined. In a multivariable analysis, PCNA indexes were significantly associated with tumor stage (p=0.024), whereas AgNORs scores were not significantly associated with the stage or histopatholgic features of the tumors. Histologic grade was correlated to disease stage at a significant level (p=0.000). But there was a trend of low tumor PCNA-indices or AgNORs counts with survival advantage for patients, but this did not reach statistical significance. The results suggest that the fraction of PCNA positive nuclei would be useful for investigating the malignant potential of renal pelvic cancers, although their clinical use as markers of biologic behavior may be limited.

The Relationship of Ki-67, Proliferating Cell Nuclear Antigen, AgNORs and p53 Protein Expression in Astrocytoma.: Dong Ja Kim, Jae Weon Lim, Yoon Kyung Sohn; Korean J Pathol. 1999;33(1):25-31.

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Abstract PDF: The grading of astrocytoma has traditionally relied on histological assessment, but there are some differences in their parameters, application, and reproducibility. Recently, numerous studies have attempted to correlate biological aggresiveness with tumor proliferation index using new immunohistochemical methods. The purpose of this study is to correlate the histopathological grades of astrocytoma with the expression of Ki-67, PCNA, p53 protein and AgNORs. The paraffin sections of 41 consecutive cases of astrocytomas were examined. Histologically the tumors were graded as three groups under the St. Anne-Mayo system and showed 14 cases in grade II, 15 cases in grade III and 12 cases in grade IV (glioblastoma multiforme). As a result, the Ki-67 labelling index and p53 protein expression tended to increase with increasing grade of malignancy. But the univariate analysis showed that there was no significant difference between the tumor grades (p>0.05). The PCNA labelling index and number of AgNORs revealed striking differences between the grade II and grade III astrocytomas (p<0.05). We concluded that the PCNA labelling index and AgNORs counting are useful markers for differentiation between grade II and III astrocytomas.

The Significance of AgNOR Count in Body Fluid: Differential between reactive mesothelial cells & malignant cells.: Seung Sam Paik, Eun Kyung Hong, Se Jin Jang, Moon Hyang Park, Jung Dal Lee; Korean J Cytopathol. 1997;8(2):129-134.

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Abstract PDF: To distinguish reactive mesothelial cells from malignant cells in body fluid, we applied silver staining of nucleolar organizer regions(AgNORs) to ethanol fixed cytologic preparations. Fifty aspirated samples of benign(22 cases) and malignant(26 cases) body fluids were studied using the one step silver staining method. Two cytologically atypical samples were also included in the study. In malignant cases the mean AgNOR count was 3.56+/-0.81, while in benign cases the mean AgNOR count was 2.02+/-0.33. The difference of AgNOR counts between these two groups were statistically significant(p<0.001). The mean of atypical cases was 2.91. Both were diagnosed as malignant in follow-up cytology. In malignant effusions, there is statistically significant difference in AgNOR counts between cells forming complex papillae or clusters and singly scattered cells(p<0.05), 3.29+/-0.95 and 3.83+/-0.55, respectively. We concluded that AgNOR count appears to be useful as a diagnostic tool especially when the cytologic differentiation is difficult.

A Study of the Correlation between Cellular Proliferating Activities and Prognosis in Gastrointestinal Stromal Tumors .: Hee Jin Chang, Duck Hwan Kim, Sung Sook Pang, Jin Hee Sohn, Jung Il Suh, In Sun Kim, Jong Sang Choi; Korean J Pathol. 1995;29(2):152-169.

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Abstract PDF: Gastrointestinal stromal tumors are notorious for their unpredictable clinical behavior. To assess the cellular proliferating activities, four different methods were used: mitotic count, nucleolar organizer region(AgNOR) staining, immunostaining of proliferating cell nuclear antigen (PCNA) and DNA ploidy were used on 39 cases of gastrointestinal stromal tumors. Additionally, we analysed cellularity, cellular atypism and necrosis. Among 39 cases of gastrointestinal stromal tumors, 11 cases were diagnosed as benign lesions according to clinicopathologic findings. Malignant lesions were arbitrarily classified into low grade(n=ll) and high grade(n=17) on the basis of absence or presence of recurrence, metastasis or tumor-related death during the follow-up period. Numbers of mitosis, AgNORs, PCNA index and DNA ploidy were correlated with grades of tumor and prognosis. Among them, AgNORs counting appeared to be the most useful in predicting prognosis. Numbers of mitosis, PCNA index and DNA ploidy showed varying degrees of overlap among the 3 groups. Among the histological parameters, cellular atypia showed some relationship with the prognosis that others did not reveal.

PCNA Labelling index and AgNORs of Transitional Cell Carcinoma of the Urinary Bladder.: Byung Gon Park, Sang Yong Lee, Mee Sook Roh, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1994;28(5):469-477.

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Abstract PDF: Proliferating cell nuclear antigen (PCNA, PC10), an auxillary protein of DNA polymerase, plays a main role in the early stage of DNA Synthesis and is synthesized from Gl phase to s phase of the cell cycle. Nucleolar organizer region (NORs) are DNA loops encoding RNA proteins(AgNORs). To evaluate correlation with PCNA labelling index (LI)and AgNORs according to histological grades and clinical stages of transitional cell carcinoma of the urinary bladder, the authors analysed 54 transitional cell carcinoma using immunohistochemical stain for PCNA and silver stain for AgNORs in paraffin sections. The comparison of PCNA (PC10) LI and clinical stage showed a significant correlation (p<0.05), where as PCNA (PC10) LI according to histologic grade showed no significant correlation. High grade tumors showed increase PCNA LI. Superficial tumors (Ta-Tl) showed significantly lower PCNA LI than muscle invasive tumors (T2-T4)(p<0.05). There was no significant correlation between AgNORs and clinical stage, bur higher stage and higher grade tumors showed increased noubers of AgNORs. These results suggest that PCNA LI has a significant correlation with clinical stages of transitional cell carcinoma of the urinary bladder.

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