Expression of the Survivin Gene in Prostate Cancer: Correlation With Clinicopathological Characteristics, Proliferative Activity and Apoptosis

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Abstract
Purpose: Although survivin expression has been reported in prostate cancer, the clinical significance of survivin expression remains unclear. To clarify the clinical significance of survivin in prostate cancer we examined survivin mRNA levels in prostate cancer tissues, and correlated these levels with parameters including the clinicopathological characteristics of patients and proliferation and apoptosis levels within prostate cancer tissues. Materials and Methods: Cancer and matched control tissues were obtained from the prostates of 150 patients who were treated with radical prostatectomy between July 1998 and December 2002. Of the 150 samples, RNA could be extracted and pathological confirmation obtained from 82 prostate cancer and 80 normal prostate samples. Polymerase chain reaction studies were performed using primers for the survivin gene with the G3PDH gene serving as control. Preoperative prostate specific antigen doubling time (PSA-DT) could be calculated for 50 patients by linear regression analysis. Immunohistochemical staining was used to study expression of proliferating cell nuclear antigen as an index of proliferative activity and single stranded DNA as an index of apoptosis. Results: Of 82 prostate cancer samples 68 (82.9%) and 47 (58.8%) of 80 control samples exhibited detectable levels of survivin mRNA. In the 65 cases in which RNA could be extracted from prostate cancer and matched control samples, the mean level of survivin expression ± SE in prostate cancer was significantly higher than that found in control tissues (0.079 ± 0.017 vs 0.025 ± 0.005, p = 0.003). The survivin expression in cancers with a short PSA-DT (less than 2 years) was significantly higher than those with a moderate PSA-DT (2 to 4 years, p <0.05) or long PSA-DT (greater than 4 years, p <0.05). In the 82 cases with prostate cancer, survivin expression was significantly higher in cancers with a high pathological T stage (p <0.05), positive lymph node metastasis (p = 0.002), positive vessel invasion (p = 0.03), positive surgical margin (p = 0.02) and high Gleason score (p <0.05). A positive correlation was present between survivin expression and proliferative activity (p = 0.005). A nonsignificant inverse association was found between survivin expression and apoptosis of prostate cancer cells (p = 0.06). Conclusions: These results suggest that the degree of survivin expression is related to the progression and aggressiveness of prostate cancer.