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 histological grade (Gleason grade) and prostate-specific antigen (PSA) mRNA expression and to evaluate the level of PSA mRNA expression as a possible prognostic marker for untreated prostate cancers. The primary grade areas of 104 prostatic biopsy specimens were analyzed for the expression of PSA mRNA and its protein by nonradioactive in situ hybridization and immunohistochemistry, respectively. A multivariate survival analysis was performed to examine the correlation between PSA mRNA expression and several clinicopathological parameters, e.g., the immunostaining level of PSA protein in biopsy specimens. The percentage of specimens positive for PSA mRNA increased significantly with advanced histological 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 histological grade (P < 0.0001). Only 26.0% of specimens positive for PSA protein were also positive for PSA mRNA (and vice versa, 6.7%). Other tumors were either positive for both (66.3%) or negative for both (1.0%). When 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 either primary or secondary grade) area of tumors were at high risk for cancer-related death (P = 0.017). Furthermore, in cancer-specific survival curves based on PSA mRNA expression status, patients with high levels of PSA mRNA expression in the higher grade area of tumors had a significantly poorer prognosis (P = 0.001), compared with those with tumors expressing low levels of PSA mRNA. Our results suggested that analysis of PSA mRNA expression in specific areas in biopsy specimens of patients with untreated prostate cancer may provide a good assessment of prognosis of prostate cancers.