Microvessel density, p53, retinoblastoma, and chromogranin a immunohistochemistry as predictors of disease-specific survival following radical prostatectomy for carcinoma of the prostate

Objectives. Angiogenesis has been shown to be related to p53 and retinoblas toma gene function as well as to neuroendocrine differentiation (as measure d by chromogranin A staining) in prostate tumors. Studies have indicated th at immunohistochemical assessment of p53, retinoblastoma, and chromogranin A in prostate cancers treated by radical prostatectomy can be useful in pre dicting disease-specific survival, whereas the degree of microvessel densit y (MVD), a measure of angiogenesis, correlates with disease recurrence. The ability of MVD, however, to predict disease-specific survival either alone or in conjunction with other prognostic factors has not yet been evaluated . The purpose of our study was to determine the relative importance of p53, retinoblastoma, and chromogranin A as well as MVD in the prediction of dis ease-specific survival following radical prostatectomy in conjunction with classical pathologic assessment. Methods. From 1970 to 1984, radical prostatectomy was performed on 75 patie nts with clinical Stage A2 to B2 adenocarcinoma of the prostate. No neoadju vant or adjuvant treatments were given, and patients were followed until de ath. Prostatectomy specimens were examined to evaluate conventional patholo gic parameters. In addition, the tissue was immunohistochemically stained f or p53, retinoblastoma, chromogranin A, and endothelial cells. A previously described computerized imaging system analyzed the microvessels and comput ed both "optimized" and "area-weighted" MVD scores. Proportional hazard mod els were used to investigate the simultaneous association of these variable s with disease-specific survival. Results. Of the 75 patients, 4 had follow-up of less than 3 months, and 29 patients had inadequate tissue for analysis of all immunohistochemical mark ers. The analyzed subset of 42 patients was found to he representative of t he cohort of 71 patients. Multivariate analysis revealed that p53 and retin oblastoma have the greatest prognostic importance regarding disease-specifi c survival. Chromogranin A and optimized or area-weighted MVD scores were o f no additional value when p53 and retinoblastoma were assessed. Conclusions. Microvessel density, as a determinant of angiogenesis and chro mogranin A, does not seem to add significantly to the prognostic disease-sp ecific survival information provided by conventional pathology combined wit h p53 and retinoblastoma assessment. UROLOGY 55: 743-749, 2000. (C) 2000, E lsevier Science Inc.