Cell Proliferation in Prostatic Adenocarcinoma: In Vitro Measurement by 5-Bromodeoxyuridine Incorporation and Proliferating Cell Nuclear Antigen Expression

Abstract

We assessed cancer cell proliferation, a marker of the biologic activity of tumor cells, by evaluating bromodeoxyuridine (BrdUrd) incorporation and proliferating cell nuclear antigen (PCNA) expression. Prostatic carcinoma specimens (N = 48) were incubated in the presence of BrdUrd to label cells undergoing DNA synthesis, and immunocytochemical staining was performed with monoclonal antibodies to BrdUrd and PCNA and a standard indirect immunoperoxidase technique. The proportion of cells staining positively (labeling index or LI) for BrdUrd and PCNA was determined in 2 ways: by counting only high-power fields with the greatest concentration of stained cells (selected LI); or by counting cells in random fields (random LI). For BrdUrd the mean selected and random LIs were 3.08% and 1.62%, respectively; for PCNA they were 6.02% and 3.47%. Random and selected BrdUrd correlated well (r2 = 0.83), as did random and selected PCNA LIs (r2 = 0.86). However, a weaker correlation was noted when LIs of both techniques were compared, with the PCNA LI usually higher. The LIs of either technique correlated rather poorly with tumor grade and concentration of prostate-specific antigen, but correlated well with clinical stage as assessed by examination and imaging. In addition, either technique discriminated among tumors known to be pathologically confined (stages A and B) and those with extension to seminal vesicles (stage C) or metastatic to regional lymph nodes or bone (p < 0.019).