EXPRESSION OF CELL-CYCLE-REGULATED PROTEINS IN PROSTATE-CANCER

Markers of cellular proliferation have proven to be useful prognostic markers in several tumor types. Recently, immunoreactivity for cyclins was found to provide an independent marker of tumor proliferation in breast cancer. In this study, we sought to determine the pattern of im munoreactivity for cyclins A, B, E, and Ki-67 in surgically resected p rostate cancer and to determine their possible prognostic significance , Twenty-eight tumors of American Urological Association stages B and C were selected for study, Immunoreactivity for cyclins A and B was de tected in most tumors and was present at significantly reduced levels as compared with breast cancer, Staining for cyclin E was present in f our tumors and was present only in focal areas in two of the four, Suc h focal variation in expression of cell cycle regulators may reflect g enetic instability in a tumor. Immunoreactivity for cyclins A and B wa s correlated with both Ki-67 index (the percentage of cells with Ki-67 immunoreactivity) and with each other, A Ki-67 index greater than 4.0 was associated with shorter time to prostate-specific antigen-detecte d relapse (P = 0.026), The fraction of cells staining for cyclins A an d B divided by the fraction of cells staining for Ki-67 [(A + B)/K] wa s highly predictive of relapse, with values less than 0.50 associated with more rapid progression (P < 0.001). This latter result remained s tatistically significant after controlling for Gleason score by strati fication, Our results suggest that immunoreactivity for markers of cel lular proliferation may provide useful prognostic information in local ized prostate cancer, and they need to be validated in a larger number s of patients.