Microvessel density, p53, retinoblastoma, and chromogranin A immunohistochemistry as predictors of disease-specific survival following radical prostatectomy for carcinoma of the prostate.
OBJECTIVE
Angiogenesis has been shown to be related to p53 and retinoblastoma gene function as well as to neuroendocrine differentiation (as measured by chromogranin A staining) in prostate tumors. Studies have indicated that immunohistochemical assessment of p53, retinoblastoma, and chromogranin A in prostate cancers treated by radical prostatectomy can be useful in predicting disease-specific survival, whereas the degree of microvessel density (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 disease-specific survival following radical prostatectomy in conjunction with classical pathologic assessment.


METHODS
From 1970 to 1984, radical prostatectomy was performed on 75 patients with clinical Stage A2 to B2 adenocarcinoma of the prostate. No neoadjuvant or adjuvant treatments were given, and patients were followed until death. Prostatectomy specimens were examined to evaluate conventional pathologic parameters. In addition, the tissue was immunohistochemically stained for p53, retinoblastoma, chromogranin A, and endothelial cells. A previously described computerized imaging system analyzed the microvessels and computed both "optimized" and "area-weighted" MVD scores. Proportional hazard models were used to investigate the simultaneous association of these variables 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 markers. The analyzed subset of 42 patients was found to be representative of the cohort of 71 patients. Multivariate analysis revealed that p53 and retinoblastoma have the greatest prognostic importance regarding disease-specific survival. Chromogranin A and optimized or area-weighted MVD scores were of no additional value when p53 and retinoblastoma were assessed.


CONCLUSIONS
Microvessel density, as a determinant of angiogenesis and chromogranin A, does not seem to add significantly to the prognostic disease-specific survival information provided by conventional pathology combined with p53 and retinoblastoma assessment.
Krupski
T
T
Department of Urology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Petroni
G R
GR
Frierson
H F
HF
Theodorescu
J U
JU
D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry* / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002196:Capillaries; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016160:Retinoblastoma Protein / Q000032:analysis*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53