Relation of endocrine‐paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate

Abstract

The relative distribution pattern of the pan-endocrine marker Chromogranin A (Chr A) and the proliferation-associated Ki-67 antigen was investigated in 20 prospectively sampled prostatectomy specimens. In cryostat sections, the Chr A immunoreactivity showed evidence of endocrine differentiation in all 15 prostatic adenocarcinomas. Nine tumors displayed a weak, 5 a moderate, and 1 adenocarcinoma a strong endocrine differentiation. These findings highlight the importance of endocrine differentiation in prostate malignancy that histologically resembles ordinary adenocarcinomas. The simultaneous demonstration of Ki-67 and Chr A revealed that in normal, hyperplastic, and neoplastic prostate tissue Chr A-positive cells were preferentially situated in proximity to Ki-67-labeled cells. This relative distribution pattern of both markers may indicate that endocrine cells are involved in controlling cell proliferation through a paracrine hormonal mechanism. However, an obvious correlation was not found between the degree of endocrine differentiation and proliferative activity in prostatic adenocarcinomas. Furthermore, a coexpression of Ki-67 and Chr A in the same (tumor) cells was not observed suggesting that the endocrine phenotype is only expressed in the G0 phase of the cell cycle as well as in normal, hyperplastic, and neoplastic conditions.

NE-10 Neuroendocrine Cancer Promotes the LNCaP Xenograft Growth in Castrated Mice

“…NE differentiation in prostate adenocarcinoma is usually manifested as isolated foci or islands of cells expressing certain NE-related products (23). Using double label techniques in human tissue, Bonkhoff et al (5,6) reported that increased proliferation in exocrine cells surrounded NE tumor cells. Peptide growth factors and cytokines, operating either within the context of androgen-dependent signaling mechanisms or in an androgen-independent context, are likely to be critical to the process of prostate cancer progression.…”

“…Malignant neoplasia of the prostate with NE differentiation has poorer prognosis (35% survival rate in 2 years) compared with cases without it (97% survival rate in 2 years; Refs. 5,6). Histological studies reveal that NE cells are significantly more abundant in cancerous than in noncancerous tissues (7).…”

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

“…These neuroendocrine features include the appearance of neuroendocrine cell foci surrounded by proliferating epithelial cells (3). Because neuroendocrine prostate cells in normal, hyperplastic, or cancerous tissue secrete many neuropeptides with mitogenic activities like parathyroid hormone-related peptide, calcitonin, or gastrin-related peptides, it has been proposed that paracrine secretion of neurosecretory products released by neuroendocrine cells could be responsible for the progression of cancer toward an androgen-independent stage (for review, see Ref.…”

Vascular endothelial growth factor (VEGF) expression in prostatic tumours and its relationship to neuroendocrine cells

“…They express prostate-specific antigen (PSA) (Aprikian et al, 1993;Cohen et al, 1992) and are believed to represent a third epithelial type originating from a common stem cell. As these cells do not appear to proliferate (Bonkhoff et al, 1991), it is assumed that the increased numbers seen in the tumours originate from prostatic carcinoma cells which are induced to undergo neuroendocrine differentiation. Prostatic neuroendocrine cells lack androgen receptor and it has been suggested that they could represent an androgen-insensitive cell population that can expand in some cases to populate the tumour (Krijnen et al, 1993 (Chaudhry et al.…”