Neuroendocrine cells in prostate cancer correlate with poor outcomes: a systematic review and meta‐analysis

Abstract

To perform a systematic review and meta-analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of reporting neuroendocrine staining at diagnosis on patient outcomes. MethodsMedical databases were searched to identify studies in which adenocarcinoma specimens were stained with any of the following four neuroendocrine markers: chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin and CD56. The prevalence of neuroendocrine staining and correlation of the prevalence of neuroendocrine staining to patient outcomes were analysed using a random-effects model. All statistical tests were two-sided. ResultsSixty-two studies spanning 7616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to that of NSE (39%) and higher than that of synaptophysin (31%). The prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.49 to 2.65) and poorer prostate cancer-specific survival (HR 7.03, 95% CI 2.55 to 19.39) compared to negative patients, even among those with low-risk cancers. ConclusionDiscrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies are needed to determine the exact quantifiable thresholds for use in reporting neuroendocrine cell staining to identify patients at higher risk of progression.

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort

“…In a recent systematic review, Kannan et al have evaluated the role of CgA IHC in patients with PCa. 18 response to androgen deprivation therapy due to the absence of the androgen receptor in neuroendocrine cells resulting in a poor prognosis for these patients. Moreover, it has been suggested that neuroendocrine differentiation may be one of the many mechanisms behind castration-resistant development.…”

“…The present study has been performed in a selected cohort of patients with localized/locally advanced disease with negative IHC and therefore the results apply to the enrolled population. In a recent systematic review, Kannan et al have evaluated the role of CgA IHC in patients with PCa 18 . According to their results CgA IHC may vary between 4% and 100% underlying the high variability of CgA expression.…”

“…In a recent systematic review, Kannan et al have evaluated the role of CgA IHC in patients with PCa. 18 | 3…”

The LncRNA DUXAP10 Could Function as a Promising Oncogene in Human Cancer

“…It is now widely accepted that the early diagnosis (An et al, 2021;Kannan et al, 2021) of tumors is essential for achieving a better prognosis and a lower mortality rate. Accurate diagnostic biomarkers (Ott et al, 2009;Wardle et al, 2015;Dragani et al, 2020) for detecting early-stage tumors are of great clinical significance.…”

“…And poor quality of life, especially cancer (Lee et al, 2018;Moliner et al, 2019;Sidney et al, 2019;Mulder et al, 2021;Su et al, 2021). Cancer (Mohsen et al, 2014;Christensen et al, 2018;Kannan et al, 2021;Mokgautsi et al, 2021) has become one of the most common causes of death worldwide, and the identification of cancer-related targets and relevant carcinogenesis mechanisms for patients at the early stage of the disease are urgently needed (Saha et al, 2019;Jiang et al, 2020;Brennan and Smith, 2021;Hua et al, 2021;Jones et al, 2021).…”