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Expression of Cell Cycle-regulated Proteins in Prostate Cancer¹

Division of Molecular Oncology [R. D. M., A. D.], Department of Pathology [S. L., C. C., R. C.], and the Division of Urology, Department of Surgery [J. R.], Brigham and Women's Hospital, and Divisions of Medical Oncology [R. D. M.] and Biostatistics [K. P.], Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

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 immunoreactivity for cyclins A, B, E, and Ki-67 in surgically resected prostate 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 detected in most tumors and was present at significantly reduced levels as compared with breast cancer. Staining for cyclin E was present in four tumors and was present only in focal areas in two of the four. Such focal variation in expression of cell cycle regulators may reflect genetic instability in a tumor. Immunoreactivity for cyclins A and B was 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-detected relapse (P = 0.026). The fraction of cells staining for cyclins A and B divided by the fraction of cells staining for Ki-67 [(A + B)/K] was highly predictive of relapse, with values less than 0.50 associated with more rapid progression (P < 0.001). This latter result remained statistically significant after controlling for Gleason score by stratification. Our results suggest that immunoreactivity for markers of cellular proliferation may provide useful prognostic information in localized prostate cancer, and they need to be validated in a larger numbers of patients.

¹ This work was supported by grants from the National Cancer Institute (to R. D. M.), the American Cancer Society (to A. D.), and the Massachusetts Department of Public Health (to A. D.).

² To whom requests for reprints should be addressed, at Department of Pathology, Thorn 530, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. Phone: (617) 278-0468; Fax: (617) 732-7449; E-mail: adutta@bics.bwh.harvard.edu.

Received 3/12/96. Accepted 7/15/96.

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