Neuroendocrine differentiation does not have independent prognostic value in conservatively treated prostate cancer

Abstract

In vitro studies have implicated neuroendocrine differentiation in the development of hormone resistant prostate cancer following administration of androgen blockers. Studies on clinical material are equivocal. We wished to understand the significance of neuroendocrine differentiation in our large and well-characterised cohort of clinically localised prostate cancer, treated conservatively. Immunohistochemical expression of chromogranin-A was assessed semi-quantitatively on tissue samples of 806 patients in a tissue microarray approach. The correlation of expression with 10-year prostate cancer survival was examined. Multivariate analysis including contemporary Gleason score was performed and sub-group analysis of early hormone treated patients was also undertaken. Chromogranin-A expression correlated with high Gleason score (χ(2) = 28.35, p < 0.001) and early prostate cancer death (HR = 1.61, 95 %CI = 1.15-2.27, p < 0.001). In univariate analysis, NE differentiation correlated significantly with outcome (HR = 1.61, 95 % CI 1.15-2.27, p < 0.001) However in multivariate analysis including Gleason score, chromogranin-A expression was not an independent predictor of survival (HR = 0.97, 95 %CI = 0.89-1.37, p = 0.87). Although chromogranin-A expression was higher in patients with early hormone therapy (χ(2) = 7.25, p = 0.007), there was no association with prostate cancer survival in this sub-group (p = 0.083). Determination of neuroendocrine differentiation does not appear to have any bearing on the outcome of prostatic carcinoma and does not add to the established prognostic model.

Clinical and molecular features of treatment‐related neuroendocrine prostate cancer

“…Until recently, there has been considerable debate regarding the definition and classification of NEPC, which has resulted in contradictory reports regarding its clinical significance . In 2013, the Prostate Cancer Foundation assembled a working committee to address this issue and proposed a new pathological classification of NEPC .…”

“…Until recently, there has been considerable debate regarding the definition and classification of NEPC, which has resulted in contradictory reports regarding its clinical significance. 12,16 In 2013, the Prostate Cancer Foundation assembled a working committee to address this issue and proposed a new pathological classification of NEPC. 17 The new classification consisted of: (i) usual prostate adenocarcinoma with NE differentiation; (ii) adenocarcinoma with Paneth cell NE differentiation; (iii) carcinoid tumor; (iv) small cell carcinoma; (v) LCNEC; and (vi) mixed NE carcinoma-acinar adenocarcinoma.…”

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

“…Typical markers used to identify neuroendocrine differentiation (NED) in tumor tissue are neuron specific enolase (NSE), chromogranin A (CgA) and synaptophysin (Syp). 1 - 3 Neuroendocrine differentiation, measured by one or more of those markers, has been associated with disease progression 4 or poor survival in prostate cancer 5 , but up to now its prognostic value has not been clarified because of controversial results 6 ; 7 , 8 . However, Epstein et al 9 have recently suggested using neuroendocrine markers to better characterize and classify NED in prostate cancer.…”

Molecular markers to guide primary radical treatment selection in localized prostate cancer

“…This has allowed precise examination of p53, CD147 and other markers in the context of structural rearrangements in prostate cancer as well as robust validation of new findings [99,100]. Other groups have similarly, through large consortia (notably the transatlantic group), exploited archival clinical tissue to produce large tissue arrays for biomarker studies [101,102]. These arrays have been based usually on surgically derived samples from RP or transurethral resection because of the abundance of tissue.…”