Proliferating cell nuclear antigen expression and its relationship to malignancy potential in invasive colorectal...

Cellular proliferative activity is a useful indicator of biologic aggressiveness in colorectal carcinoma. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) has important advantages of maintaining tissue architecture and technical simplicity. The aim of this study was to investigate the correlation between proliferative activity and malignancy potential in colorectal carcinomas to determine whether proliferative index of cancer cells has prognostic significance using immunohistochemical technique.

Proliferation index at the invasive tumor margin of 86 paraffin sections of advanced colorectal carcinomas was assessed by immunohistochemical study using a mouse monoclonal antibody to PCNA (PC-10) and was compared with conventional clinicopathologic factors and other possible prognostic parameters, including p53 overexpression, tissue carcinoembryonic antigen immunoreactivity pattern, and flow cytometric DNA ploidy. In addition, recurrence and survival were analyzed in accordance with degree of PCNA expression.

PCNA labeling index (PCNA-LI) increased significantly as the Astler-Coller stage advanced (P = 0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P = 0.0027), lymphatic invasion (P = 0.0001), vascular invasion (P = 0.0001), lymph node metastasis (P = 0.0001), and liver metastasis (P = 0.0036). Mean PCNA-LI was also significantly higher in tumors with DNA aneuploidy (P = 0.0006) and negative and cytoplasmic patterns of carcinoembryonic antigen immunoreactivity (P = 0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P < 0.01), and four-year survival rates for both overall and curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P < 0.005 and P < 0.01, respectively).

Evaluation of PCNA-LI at the invasive tumor margin in colorectal carcinomas is suggested to be valuable in predicting those people with a higher potential for metastasis and recurrence after surgery; thus, the evaluation is helpful in planning reasonable adjuvant therapy, even in the earlier stages.