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.
A 3-tier histopathologic scoring system, the chemotherapy response score (CRS), was previously devised for reporting the histologic response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIc/IV tuboovarian high-grade serous carcinoma. This has been shown to predict the outcome and offer additional information to other methods of assessing the treatment response. In the present study, the reproducibility of this scoring system was assessed by determining the interobserver agreement among reporting pathologists. A total of 5 groups each comprising 3 pathologists with different levels of expertise were selected. The participants underwent an online tutorial on how to apply the CRS system. 40 cases (38 cases in 2 appraiser groups) were scored individually by each of the 15 pathologists. The interobserver reproducibility was calculated using Fleiss' κ, Kendall's coefficient of concordance, and the absolute agreement between (a) individual pathologists within 1 group, (b) with the majority score agreement between all groups, and (c) with all individual scores. The CRS system was found to be highly reproducible among all the pathologists' groups (κ=0.761). The agreement in identifying the group of patients with the best response to chemotherapy was exceptionally high (κ=0.926). We conclude that CRS has a high interobserver reproducibility, especially in identifying the subgroup of patients with the best chemotherapy response, justifying its inclusion in clinical trials and reporting practice.
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