THE CLINICAL PREDICTIVITY OF BIOMARKERS OF STAGE III-IV EPITHELIAL OVARIAN-CANCER IN A PROSPECTIVE RANDOMIZED TREATMENT PROTOCOL

BACKGROUND. The aim of this study was to define the clinical relevance of functional biomarkers, prospectively assessed in a randomized clin ical protocol, in patients with Stage III-IV epithelial ovarian cancer . The protocol compared cisplatin with polychemotherapy that included cisplatin and cyclophosphamide. METHODS. In a subset of 168 patients w ith invasive epithelial ovarian cancer cell proliferation was determin ed by the H-3-thymidine labeling index, DNA ploidy was assessed by flo w cytometry, and the expression of p53, bcl-2, and glutathione S-trans ferase-pi (GST-pi) was evaluated by immunohistochemistry using the ant ibodies PAb1801, anti-bcl-2, and GST-pi, respectively. RESULTS. Cell p roliferation, DNA ploidy, and the expression of p53, bcl-2, and GST-pi were generally unrelated to one another and unrelated to clinicopatho logic features, except for an association between DNA ploidy and the r ate of cell proliferation. All biologic variables except bcl-2 were sl ightly related to tumor grade. DNA ploidy emerged as a predictor of cl inical complete response and 3-year overall survival, regardless of tr eatment type or residual disease. Conversely, except for a favorable o utcome for patients with tumors not expressing bcl-2 who were treated with cisplatin, no definitive patterns of predictivity for short term or long term clinical outcomes were observed for the other biomarkers studied. CONCLUSIONS. DNA ploidy appears to be the most clinically rel evant biomarker for epithelial ovarian cancer, More information is nee ded to understand the role of the other markers studied in this tumor type. (C) 1998 American Cancer Society.