The prognostic influence of neuroendocrine cells in prostate cancer: Results of a long‐term follow‐up study with patients treated by radical prostatectomy

Abstract

The distribution of immunohistochemically defined neuroendocrine (NE) cells in benign, pre-cancerous and neoplastic prostatic tissues and the prognostic value of these cells in prostate cancer were studied in the radical prostatectomy specimens of 90 patients from whom complete long-term follow-up data were available. The tissue blocks containing all the different Gleason patterns observed in a particular tumor were selected and immunostained. Since chromogranin B stained only a few cells compared to chromogranin A (CgA), NE cells were only defined by their reactivity with CgA. A semi-quantificative CgA score was assessed for all distinct pathological areas. Cox's regression model was used to analyze the influence of final TNM classification (TNM, 1992), Gleason sum score (GSS), age and CgA score on the probability of progression and tumor-specific death. NE cells were demonstrated in all normal prostatic tissues and in most hyperplastic and intra-epithelial neoplastic lesions. CgA staining was seen in 78% of the tumors. CgA scores were not related with Gleason growth patterns, GSS or TNM classification and had no prognostic value. The independent prognostic variables in Cox's regression model were: GSS and pT stage for progression and GSS for tumor-specific survival. Theoretically, NE cells could influence tumor behavior and this discrepancy suggests the need for experimental studies to investigate the role of NE cells in the normal and neoplastic prostate.

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

“…In accordance with observations made for other markers, 31 we did not find a correlation between PAM or PAMP expression and GSS for either group of RPs or the TURPs. PAMP-or PAMassociated NE differentiation does not appear to be directly associated with tumor grade and, furthermore, does not have clinical value for estimating prognosis.…”

“…31 Tissue sections adjacent to slides immunostained for PAMP or PAM were stained with hematoxylin and eosin and the neoplastic zones present in every tissue identified and marked. These marks were copied on the corresponding immunolabeled slides.…”

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease

“…In the majority of published studies, CgA immunostaining in tumor specimens obtained after radical prostatectomy failed to show a prognostic role (Noordzij et al 1995, Bubendorf et al 1997, Abrahamsson et al 1998, Ahlgren et al 2000, Bostwick et al 2002. Similarly, Lilleby et al (2001) did not show a significant correlation between elevated circulating CgA values and prognosis in a patient subset with hormone-naive disease submitted to radiotherapy.…”

“…These findings notwithstanding, the relationship with survival is still controversial, since some studies demonstrated a negative prognostic role (Weinstein et al 1996, McWilliam et al 1997, Theodorescu et al 1997, while others did not (Noordzij et al 1995, Bubendorf et al 1997, Abrahamsson et al 1998, Ahlegren et al 2000, Bostwick et al 2002. All these studies involved hormonenaive patients.…”

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

“…However, we found no significant differences in age, pre-biopsy serum PSA value, Gleason score, EOD grade, T stage or N stage between the Cg A-positive and Cg A-negative groups. Noordzji et al (18) and Isshiki et al (11) also found no significant differences or correlation in Gleason score or pathological stage with NE cell differentiation.…”