Intensity of stromal changes is associated with tumor relapse in clinically advanced prostate cancer after castration therapy

Abstract

Reactive stromal changes in prostate cancer (PCa) are likely involved in the emergence of castration-resistant PCa (CRPC). This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade (Masson stain 82.8% vs 45.6%, P < 0.001) and vimentin expression (P = 0.005) were significantly higher, and desmin expression (P = 0.004) significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 (P = 0.009). Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse (hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012). These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.

Figure 1

Stromal cell phenotype in prostate cancer detected by (a) Masson trichrome staining (×200), (b) vimentin (×100), and (c) desmin (×100). Scale bars = 20 μm.

Figure 2

Distribution of reactive stroma in tumors with different Gleason score. (a) Stroma grade in the tumors with Gleason score of 6–7, (b) Stroma grade in peritumoral tissue with Gleason score of 6–7, (c) Stroma grade in the tumors with Gleason score of 8-9, (d) Stroma grade in peritumoral tissue with Gleason score of 8–9.

Figure 3

Kaplan-Meier analysis showed a significant association between intensity of reactive stroma and the occurrence of castration-resistant prostate cancer in tumors with Gleason score of 6–7 (log-rank P = 0.009, (a). Patients with higher vimentin expression (log-rank P = 0.044, (b) or lower desmin expression (log-rank P = 0.045, (c) had a shorter disease-free period.