The histogenesis of small cell carcinoma of the prostate an immunohistochemical study

Schron, Deborah; Gipson, Thomas; Mendelsohn, Geoffrey

doi:10.1002/1097-0142(19840601)53:11<2478::aid-cncr2820531119>3.0.co;2-q

Cited by 106 publications

(55 citation statements)

References 14 publications

(1 reference statement)

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“…Differences were, however, found for the NE markers. ChrA expression decreased with increasing malignancy, being highest in NETs (80-90% LI) and lowest in high-grade NECs, with only some isolated tumor cells positive for ChrA [1,2,16,17,20,21,22]. The staining intensity of SNP was strong in NETs and in high-grade NECs, with 50-75% of the tumor cells showing positivity for SNP.…”

Section: Discussionmentioning

confidence: 96%

“…Our knowledge about the histogenesis of neuroendocrine tumors (NETs) is incomplete and includes theories that vary from organ to organ [3,6,10,12,18,19,20,22]. NETs and well-differentiated neuroendocrine carcinomas (low-grade NECs) are believed by some authors to arise from orthotopic NE cells of the epithelium of the respective organs [6,17,18].…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs

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Köllermann

2001

Virchows Archiv

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Small-cell neuroendocrine carcinomas (NECs) of the prostate are believed not to derive from benign orthotopic NE epithelial cells. Instead, an origin from a putative stem cell is actually the most favored concept. Whether this concept can also be applied to neuroendocrine tumors (NETs) of other organs, especially whether there are indications for well-differentiated NET-NEC sequence, is subject of the present study. A double-labeling technique for the proliferation marker MIB-1 and the NE markers chromogranin A (ChrA) and synaptophysin (SNP) was used for the immunohistochemical analysis of 45 well-differentiated NETs, 16 well-differentiated (low-grade) NECs, and 63 high-grade NECs of the esophagus, stomach, small intestine, appendix, colon, lung, prostate, and urinary bladder. The lowest proliferative activity was found in NETs (0.85% of tumor cells), and the highest activity was found in high-grade NECs (72.5%). The expression of ChrA was highest in NETs and lowest in high-grade NECs. None of the NETs and only sporadic cells in low-grade NECs showed double labeling (up to 0.05%). Up to 50% of the tumor cells in high-grade NECs were positive for MIB-1 and SNP. The percentage of double-labeled cells ranged between 0.9 and 39.6 (mean 9.7). No double-labeled cells were found in the normal epithelium adjacent to the tumors. Transitions from NET to NEC could not be observed. NETs and low-grade NECs differ in their proliferative activity from high-grade NECs, suggesting that they may arise from different precursor cell populations.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs

Helpap

Köllermann

2001

Virchows Archiv

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“…This common feature suggests a close relationship between the two cell types. Some authors have speculated on the multidirectional differentiation of a prostatic stem cell into either secretory epithelial cells or neuroendocrine cells (Schron et al 1984;DeLellis et al 1984;Roy et al 1987). Further experimental studies should be designed with the aim of identifying and characterizing the factors involved in the induction of neuroendocrine differentiation in prostatic epithelium.…”

Section: Discussionmentioning

confidence: 99%

Do neuroendocrine cells in human prostate cancer express androgen receptor?

et al. 1993

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Abstract. The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy.

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“…6 There are a number of theories that suggest a point of origin for these cells. 10 One theory postulates that NE differentiation originates from neural crest cells, 11,12 which give rise to cells containing neurosecretory granules known as 'amine precursor uptake decarboxylase'; another theory postulates that these cells could be the final dedifferentiation product of typical adenocarcinoma, based on a model of 'divergent differentiation'. 13 This model suggests that NE cells might be derived from adenocarcinoma cells by a process of transdifferentiation, in response to microenvironmental changes in the hormonal and growth factor milieu.…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of neuroendocrine differentiation in prostate cancer, putting together the pieces of the puzzle

Berruti

Vignani²,

Russo³

et al. 2010

RRU

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Neuroendocrine (NE) differentiation is a common feature in prostate cancer (PC). The clinical significance of this phenomenon is controversial; however preclinical and clinical data are in favor of an association with poor prognosis and early onset of a castrate resistant status. NE PC cells do not proliferate, but they can stimulate the proliferation of the exocrine component through the production of paracrine growth factors. The same paracrine signals may favor the outgrowth of castrate adapted tumors through androgen receptor dependent or independent mechanisms. Noteworthy, NE differentiation in PC is not a stable phenotype, being stimulated by several agents including androgen deprivation therapy, radiation therapy, and chemotherapy. The proportion of NE positive PC, therefore, is destined to increase during the natural history of the disease. This may complicate the assessment of the prognostic significance of this phenomenon. The majority of clinical studies have shown a significant correlation between NE differentiation and disease prognosis, confirming the preclinical rationale. In conclusion the NE phenotype is a prognostic parameter in PC. Whether this phenomenon is a pure prognostic factor or whether it can influence the prognosis by favoring the onset of a castrate resistance status is a matter of future research.

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The histogenesis of small cell carcinoma of the prostate an immunohistochemical study

Cited by 106 publications

References 14 publications

Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs

Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs

Do neuroendocrine cells in human prostate cancer express androgen receptor?

Prognostic role of neuroendocrine differentiation in prostate cancer, putting together the pieces of the puzzle

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