Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate

Abstract

Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2‐year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron‐specific enolase (NSE), thyroid‐stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate‐specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA‐positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA‐positive NE cells. During the 2‐year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period. P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells. Prostate 31:110–117, 1997. © 1997 Wiley‐Liss, Inc.

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

“…Nevertheless, Schmid and colleagues (Schmid et al 1994) reported that CgB is the major component, whereas CgA is virtually absent in 17 poorly differentiated prostate carcinomas. Similarly, a study of 22 PCa patients revealed that the serum level of CgB but not CgA was significantly increased during a 2-year period of follow-up (Angelsen et al 1997). In cAMP-induced NE differentiation of LNCaP cells in culture, the CgA level was not altered (Bang et al 1994).…”

“…One possible explanation for the discrepancy in observations is the heterogeneity of PCa cells that can be mediated by multiple pathways to NE differentiation, leading to more than one type of cancerous NE cell (Abrahamsson 1999, Zelivianski et al 2001. Alternatively, CgA and CgB exhibit differential expression at different stages of cancer progression (Angelsen et al 1997). Further experiments are required to clarify the discrepancies.…”

La chromogranine A dans le cancer de la prostate métastatique

“…Ces auteurs ont mesuré la NSE dans le sérum de 80 patients sous traitement hormonal dont 37 présentaient des métastases, et ont relevé une NSE élevée dans 1 % des stades D0-D1, 3 à 4 % des stades D2 et aucun dans les stades D3, définis comme hormonorésistants. Les deux études d'Angelsen [9,17], publiées en 1997 avec le même groupe de 22 patients porteurs de tumeurs de la prostate T3 et T4 comprenant 12 patients métastatiques, montrent qu'en situation pré-thérapeutique la NSE n'est jamais élevée dans le sérum alors qu'elle est positive dans 77 % des tumeurs par immunohistochimie. La CgA en revanche, était positive dans 59 % des cas.…”

Androgen Deprivation Therapy and Neuroendocrine Differentiation in Prostate Carcinoma – A Possible Inductive Role

“…IAD is proposed in prostate cancer patients to delay the time to tumour progression due to castration therapy resistance. 7 Using IAD therapy, it is possible that the cyclic replacement of androgens during the 'off' therapy phases reduces the possibility of NE hyperactivation and serum CgA increase produced by CAD therapy. Using the analysis of variance, the difference between IAD and continuous CAD therapy on the overall CgA measurements only reached statistical significance in population type 1 (locally advanced tumours; p=0.001) but not in population type 2 (metastatic tumours; p=0.080).…”