The Significance of Proliferating Cell Nuclear Antigen(PCNA) and Nucleolar Organizer Regions(NORs) in Prostatic Adenocarcinoma

Suh, Jung Mo; Yoon, Jai Young; Hwang, Tae Kon

Abstract

Cell kinetic information is an important adjunct to histologically-based tumor classification. Studies on growth regulation and cellular transformation will be assisted by the identification of proteins that are synthesized in dividing cells. Proliferating cell nuclear antigen(PCNA) also known as cyclin, is a cell cycle-related nuclear protein that is maximally elevated in late G1 and S phases of proliferating cells. PCNA reacts with proliferating cells including tumor cells but gives undetectable immunofluorescence with resting cells of normal tissue. NORs are loop of DNA which occur in nucleoli and possess ribosomal DNA genes. Ribosomal DNA genes are of vital significance in the ultimate synthesis of protein, and that protein associated with NORs are stained with silver nitrate(Ag-NORs). AgNORs were studied in various tumors and may reflect the activity of cells and may be an indicator of the degree of malignancy. To evaluate the correlation between cellular proliferating activity and variable prognostic parameters, an immunohistochemical staining for PCNA and silver nitrate staining of NORs were performed in 23 cases of prostatic adenocarcinoma and 10 cases of benign prostatic hyperplasia, as control. The results were summarized as follows; 1. The mean expression of PCNA in BPH, well, moderately and poorly differentiated adenocarcinoma was 8.17+/-2.77(mean+/-SD ;n = 10), 21.75+/-6.11(n = 6), 19.40+/-6.98 (n=10) 27.93+/-8.23%(n=7), respectively in each group. Statistically significant differences were found in each group (p <0.05) except between well and moderately differentiated adenocarcinoma. 2. The mean number of Ag-NORs in BPH, well, moderately and poorly differentiated adenocarcinoma was 1.24+/-0.10(mean+/-SD;n=10), 1.87+/-0.23(n=6), 2.08+/-0.28(n=10) 4.02+/-0.22 (n = 7), respectively in each group. As the grade of tissues increased, the mean number of Ag-NORs increased too. The results showed statistically significant differences in each group (p < 0.05) except between well and moderately differentiated adenocarcinoma. 3. The mean area of Ag-NORs calculated by morphometry in BPH, well, moderately and poorly differentiated adenocarcinoma was 5.40+/-1.8um2, 7.84+/-3.68um2, 14.02+/-4.95um2, 23.9+/-6.94um2, respectively and significant differences was found statistically in each group (p < 0.05 ). 4. There was significant correlation between the expression of PCNA and the number of AgNORs(r= 0.800, p= 0.0001), the expression of PCNA and the area of AgNORs (r=0.788, p=0.0001). We concluded that the expression of PCNA and the number and area of NORs were increased with the degree of malignancy and may reflect the proliferative activity of cells in prostatic adenocarcinoma. PCNA and Ag-NORs may be a valuable prognostic indicator of patient's survival, but further studies will be needed to confirm its exact prognostic role.