EXPRESSION PROFILE OF PROSTATE-SPECIFIC ANTIGEN MESSENGER-RNA ASSESSED BY IN-SITU HYBRIDIZATION IS A NOVEL PROGNOSTIC MARKER FOR PATIENTS WITH UNTREATED PROSTATE-CANCER

The present study was undertaken to define the relationship between hi stological grade (Gleason grade) and prostate-specific antigen (PSA) m RNA expression and to evaluate the level of PSA mRNA expression as a p ossible prognostic marker for untreated prostate cancers. The primary grade areas of 104 prostatic biopsy specimens were analyzed for the ex pression of PSA mRNA and its protein by nonradioactive in situ hybridi zation and immunohistochemistry, respectively. A multivariate survival analysis was performed to examine the correlation between PSA mRNA ex pression and several clinicopathological parameters, e.g., the immunos taining level of PSA protein in biopsy specimens. The percentage of sp ecimens positive for PSA mRNA increased significantly with advanced hi stological grade. Image analysis of the signal intensity for PSA mRNA showed a significant correlation between the signal intensity in both primary and secondary grade areas of each specimen and the histologica l grade (P < 0.0001), Only 26.0% of specimens positive for PSA protein were also positive for PSA mRNA (and sice versa, 6.7%). Other tumors were either positive for both (66.3%) or negative for both (1.0%), Whe n the Cox's proportional hazards regression model was used to analyze cancer-specific survival, untreated patients with higher levels of PSA mRNA expression in the higher grade (representing higher grade of eit her primary or secondary grade) area of tumors were at high risk for c ancer-related death (P = 0.017), Furthermore, in cancer-specific survi val curves based on PSA mRNA expression status, patients with high lev els of PSA mRNA expression in the higher grade area of tumors had a si gnificantly poorer prognosis (P = 0.001), compared with those with tum ors expressing low levels of PSA mRNA, Our results suggested that anal ysis of PSA mRNA expression in specific areas in biopsy specimens of p atients with untreated prostate cancer may provide a good assessment o f prognosis of prostate cancers.