Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer

Recognition of a biologic marker in colorectal cancer tissue that correlates with recurrence and poor survival would offer a rationale for planning aggressive adjuvant therapy. This study assessed the prognostic significance of proliferation activity in cancer cells and nonneoplastic epithelial cells in patients with colorectal cancer, using proliferating cell nuclear antigen (PCNA) immunohistochemical analysis.

A mouse monoclonal antibody that reacted with PCNA was used to measure proliferation indexes in neoplastic and nonneoplastic colonic tissues of two sex-matched and age-matched groups of 40 patients with different clinical outcomes. In one group of 20 patients, there was no evidence of recurrence or residual disease after a median follow-up of 5.3 years. In the other group, all 20 patients had died within 3.6 years of recurrent disease.

The proliferation indexes in both cancer cells and epithelial cells of adjacent nonneoplastic crypts were elevated significantly in those who died compared with survivors; this finding was independent of other variables. There was evidence of an upward shift in the proliferation compartment of the normal crypt that occurred to the same extent in both patient groups. No correlation between Dukes stage and any of the proliferation indexes was observed.

Proliferation indexes in neoplastic and adjacent normal mucosa, as defined by PCNA immunohistochemical analysis, are independent predictors of recurrence and poor survival in patients with colorectal cancer, indicating that they may be helpful as predictors of long-term survival and in planning prophylactic adjuvant therapy.