Association of molecular biomarkers expression with biochemical recurrence in prostate cancer through tissue microarray immunostaining

Abstract

The aim of the present study was to investigate the prognostic role of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin-E, proliferating cell nuclear antigen (PCNA) and B cell lymphoma (Bcl)-2 in the biochemical recurrence of prostate cancer (PCa) using tissue microarray immunostaining. Tissue specimens from 128 PCa patients who underwent radical prostatectomy were processed and transferred onto tissue microarrays. The clinicopathological parameters of PCa patients were also recorded. Following immunohistochemical examination of MT-2A, E-cadherin, IL-6, cyclin-E, PCNA and Bcl-2 expression in PCa specimens, association analysis of biomarkers expression with the biochemical recurrence of PCa was performed. The results revealed that the overall rate of biochemical recurrence was 30.5% (39/128) and the median biochemical recurrence-free time was 19 months (range, 6-35 months). The biochemical recurrence rates in low-, intermediate- and high-risk PCa classification were 14.8 (8/54), 38.7 (24/62) and 58.3% (7/12), respectively. Survival analysis demonstrated that a decreased biochemical recurrence-free survival rate was noted in PCa cases with positive MT-2A and cyclin E expression as well as those with negative E-cadherin expression (P=0.022, 0.028 and 0.011, respectively). Subsequent multivariate Cox analysis revealed that MT-2A [hazard ratio (HR)=2.01; 95% confidence interval (CI)=1.08-3.15; P=0.005], E-cadherin (HR=1.79; 95% CI=1.08-2.21; P=0.042) and cyclin E (HR=1.92; 95% CI=1.22-2.45; P=0.020) were independent predictors of the biochemical recurrence of PCa. In conclusion, the present study provided clinical evidence that evaluation of molecular biomarkers expression may improve clinical prognostic accuracy for the biochemical recurrence of PCa. Of note, the expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of PCa.