OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage transitional cell carcinoma in terms of immunostaining for p53, epidermal growth factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction and to analyze the prognostic significance of these markers. STUDY DESIGN: Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell carcinomas were obtained. Selected sections of the primary tumors were immunostained for p53, epidermal growth factor receptor, and HER-2/neu; deoxyribonucleic acid ploidy and S-phase fraction were determined with use of flow cytometry. Clinical information was abstracted from the medical records. Survival times were analyzed according to the life-table methods of Kaplan and Meier, and the statistical significance of the various factors was tested with the log-rank test. The proportional hazards model of Cox was used to identify prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13 cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER-2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in 13 (45%). The S-phase fraction was ≤15% (mean) in 13 cases (45%) and >15% in 16 cases (55%). The median survival for the entire group was 52 months. None of the above variables had a significant effect on survival time. CONCLUSION: Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers. In addition, no prognostic significance was associated with these biomarkers. A study of larger numbers of cases may be more elucidative. (Am J Obstet Gynecol 1997;177:120-5)