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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine (NE) cells containing neurosecretory granules, rich in various peptide hormones and biogenic amines, are components of the human prostate epithelium and prostatic adenocarcinomas. Neuroendocrine differentiation in prostatic adenocarcinomas has been associated with a poor prognosis and, following androgen withdrawal therapy, tumor cell populations have been observed to become enriched with NE cells. We assessed androgen receptor (AR) expression in NE cells in benign and malignant prostatic tissue using double-labeling immunocytochemistry with validated monoclonal antibodies to the AR and to chromogranin A (a generic NE marker). Neuroendocrine cells in benign and malignant prostatic tissue generally showed nuclear staining with AR. Some distinct AR-negative nuclei were observed in normal NE cells. In prostatic adenocarcinomas with extensive NE differentiation, a subpopulation of AR-negative NE cells was demonstrated. In conclusion, benign and malignant prostatic tissue contain both AR-positive and AR-negative NE cells that may have significance in regards to androgen-independent tumor growth and tumor progression.
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PMID:The androgen receptor status of neuroendocrine cells in human benign and malignant prostatic tissue. 848 96

We examined retrospectively 107 step-sectioned radical prostatectomy specimens. The index tumor in each specimen was designated a transition zone carcinoma (TZCa) or a peripheral zone carcinoma (PZCa) based on its location. All tumor sections were immunohistochemically stained with chromogranin A (ChrA). A semiquantitative ChrA score (0 to 3) was assessed. ChrA-positive neuroendocrine cells were found in 83% of the index tumors. The ChrA score was significantly related to the Gleason score, the volume of the tumor, and the pathologic stage. Twenty-two percent of the index tumors were designated TZCas; 75% of these demonstrated neuroendocrine differentiation versus 85% of the PZCas. A high ChrA score of > or = 2 was found in 46% of PZCas and in only 33% of TZCas. Capsular transgression, seminal vesicle involvement, positive surgical margins, and lymph node metastasis were seen in the TZCa group in 33%, 17%, 29%, and 4%, respectively versus 58%, 20%, 48%, and 6% in the PZCa group. These findings were associated with a higher mean tumor volume in the TZCa group compared with the PZCa group. The average Gleason score of 4.5 in the TZCa group was significantly (P < 0.0001) lower than the Gleason score 6.2 in the PZCa group. Multicentricity was found in 62% of TZCas and in 49% of PZCas. Eighty-seven percent of the second tumors in the prostates with a primary TZCa were located in the peripheral zone. We conclude that the frequently occurring neuroendocrine cells population enlarges with tumor progression, especially in PZCas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphologic and neuroendocrine features of adenocarcinoma arising in the transition zone and in the peripheral zone of the prostate. 853 89

To comparatively evaluate the frequency of the neuroendocrine differentiation in the early and in the advanced stage of the disease, 189 gastric carcinomas (67 early gastric cancers and 122 advanced gastric cancers) were studied by immuno-histochemistry using a monoclonal antibody against chromogranin A (CgA). CgA-positive tumor cells were detected in 55 of 189 gastric carcinomas (29.1%). Twenty-two of 67 early gastric cancer (EGC) (32.8%), and 33 of 122 advanced gastric cancer (AGC) (27.0%) were CgA positive. The latter included 23 intestinal type, 8 diffuse type and 2 mixed type tumors. The distribution of CgA-positive tumor cells in most AGC and EGC was focal and the endocrine cells were singularly scattered in the neoplastic glands or, more rarely, grouped in small clusters. CgA-positive tumor cells, moreover, were observed in the lymph node metastases of 12 AGC and 1 EGC. Statistical analysis of data showed no significant difference in the frequency of CgA-positive endocrine cells with regard to the stage of tumor growth, histotype, sex and age. These results indicate that neuroendocrine differentiation is a phenomenon independent of tumor stage, histotype, age, and sex and that CgA-positive cells are present during the whole neoplastic progression.
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PMID:[Comparative study of endocrine differentiation in early and advanced stomach carcinoma]. 941 59

Cytokines constitute a diverse group of intercellular signaling proteins that regulate local and systemic, immune and inflammatory responses as well as wound healing and hematopoiesis. The proliferation and maturation of cells of the immune system, both normal and malignant, is regulated by cytokines such as the interleukins. Such cytokines may also influence the proliferation and differentiation of other cell types. Prostate epithelial cells differentiate along two pathways, exocrine or neuroendocrine. Elevation in the exocrine marker prostate-specific antigen and/or the neuroendocrine marker chromogranin A in serum has been associated with prostate cancer progression. Interleukin-1 (IL-1) mRNA is expressed by two androgen-insensitive (AI) but not by three androgen-sensitive prostate cancer cell lines. IL-1 inhibits while IL-2 stimulates the growth of the androgen-sensitive LNCaP cell line. Neither affects growth of AI PC-3 or DU-145 cell lines. IL-1 promotes the neuroendocrine phenotype and IL-2 promotes the exocrine phenotype in prostate cancer. The influence of the immune mediators IL-1 and IL-2 on the growth and differentiation of prostate cancer cells and its implication in tumor progression is described herein. Relationship of IL-1 with bone metastasis and the involvement of ss-2 microglobulin in the development and progression of prostate cancer are also discussed.
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PMID:Neuroendocrine and immune mediators in prostate cancer progression. 985 13

Neuroendocrine (NE) cells occur as scattered foci within prostatic adenocarcinoma, similar to their distribution within ductal epithelial cells of the normal prostate. However, the density of NE cells is often greater in prostate carcinomas than in normal tissue, and the frequency of NE cells correlates with tumor grade, loss of androgen sensitivity, autocrine/paracrine activity, and poor prognosis. Although NE cells are nonmitotic, proliferating cells are found in direct proximity to them, suggesting that NE cells provide paracrine stimuli for surrounding carcinoma cells. In vitro, differentiation of the LNCaP and PC3M prostatic tumor cell lines to a NE phenotype can be induced by dibutyryl cyclic AMP (cAMP), suggesting that physiological agents that increase intracellular concentrations of cAMP might regulate NE differentiation in vivo. Indeed, we demonstrate in this report that LNCaP cells acquire NE characteristics in response to treatment with physiological and pharmacological agents that elevate intracellular cAMP, agents such as epinephrine, isoproterenol, forskolin, and dibutyryl cAMP. The androgen-independent LNCaP-derived cell line C4-2 also responded to these agents, indicating that cells representing later stages of tumor progression are also capable of differentiation. The NE phenotype in this study was monitored by the appearance of dense core granules in the cytoplasm, the extension of neuron-like processes, loss of mitogenic activity, and expression of the NE markers neuron-specific enolase, parathyroid hormone-related peptide, neurotensin, serotonin, and chromogranin A. However, contrary to previous reports, we observed rapid loss of the NE phenotype in both LNCaP and C4-2 cells upon withdrawal of inducing agents. Withdrawal also resulted in a rapid, dramatic increase in tyrosine kinase and mitogen-activated protein kinase activities, suggesting that activation of these intracellular signaling enzymes may be important for reentry into the cell cycle. Together, these results indicate that chronic cAMP-mediated signaling is required to block proliferation of prostate tumor cells and to induce NE differentiation.
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PMID:Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: implications for prostate cancer progression. 1044 1

The theory that poorly differentiated prostate carcinoma develops a neuroendocrine (NE) phenotype is controversial. Supportive data is variable with NE expression being observed in anywhere from 5% to 83% of prostate cancers. These percentages are derived from standard immunohistochemistry studies, which make no attempt to quantify the results. High-density tissue microarrays (TMAs), represent a novel method for evaluating up to 1000 tissue samples with a 0.6 mm diameter on a single glass slide. This high throughput technology for screening antibodies, however, requires validation to determine if TMAs are useful in evaluating heterogeneously expressed proteins such as the NE markers chromogranin A (CGA) and synaptophysin (SYN). This study compares results from standard slides to TMAs in 50 primary and metastatic prostate tumors taken from 12 rapid autopsies from men with hormone refractory prostate cancer. One hundred standard and 2 TMA slides were immunostained for CGA and SYN. Using standard slides, focal NE expression was seen in 1/12 primary prostate tumors. Overall, 13/100 (13%) standard slides showed focal NE expression for both primary and metastatic prostate tumors; NE expression was observed in 4/12 autopsy cases (33%) when all tumor sites per case were considered. 458 tissue elements (tumor and normal) were arrayed into one paraffin block. Seventy-three percent (332/458) of the elements placed into the TMA were confirmed histologically to represent tumor. Seventy-five percent (250/332) and 66% (218/332) could be evaluated for CGA and SYN expression, respectively. Six of the metastatic tumors expressed CGA and SYN or 2.4% (6/250; 95% CI = 0.9% to 5.2%) and 2.3% (6/218; 95% CI = 0.8% to 5.3%), respectively. In conclusion, only focal NE expression was observed by both methods (eg, standard and TMA slides). The focal expression in these advanced prostate tumors was unexpected given data from prostate tumor cell lines and animal models suggesting that progression to the NE phenotype parallels tumor progression. This study also supports the use of high density TMAs to screen for protein expression, even when expression is focal.
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PMID:Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. 1082 85

The up-regulation of neuroendocrine (NE) differentiation after hormonal therapy, as well as the relationship between the degree of NE differentiation and androgen independence was investigated. One hundred and thirty-seven whole prostate specimens that were derived from surgery and autopsy (group A: no hormonal therapy, 44 patients; group B: with hormonal therapy less than 12 months, 25 patients; group C: with hormonal therapy more than 13 months, 68 patients) were studied. Neuroendocrine differentiation was evaluated by immunostaining with chromogranin A. The degree of NE differentiation was evaluated by the percentage area of positive NE cell expression (grade 0, negative; grade 1, 1-33%; grade 2, 34-66%; grade 3, 67-100%). The degree of NE differentiation was compared in androgen-independent and -dependent tumors in group C. Neuroendocrine differentiation was expressed as 31.8% in group A, 44% in group B and 70.5% in group C (p<0.001, Chi-squared test). Group C included 20 androgen-independent cases in which 3 cases were grade 0, 2 were grade 1, 6 were grade 2 and 9 were grade 3. Conversely, for androgen-dependent cases, there were 16, 16, 11 and 5 cases, respectively. Neuroendocrine cells, whether positive or not, alone was not significantly different (p=0.124, Chi-squared test); however, the percentage area of positive NE cell expression was significantly different between the androgen-independent and -dependent tumors (p=0.0044, Chi-squared test). Hormonal therapy may play an important role in the up-regulation of NE differentiation. As well as NE cell expression, whether positive or not, the degree of expression should also be observed to evaluate a poor prognosis, tumor progression and androgen independence.
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PMID:Up-regulation of neuroendocrine differentiation in prostate cancer after androgen deprivation therapy, degree and androgen independence. 1160 36

Recent progress in the study of chromogranins has revealed that there are many novel peptides derived from chromogranin with their multiple pathophysiologic roles. To learn the possible roles of chromogranin in breast carcinoma, we immunohistochemically investigated tissue localization of chromogranin A (CgA) and chromogranin B (CgB) in 10 normal breast tissues, 23 noninvasive ductal carcinomas (NIDCs), and 169 invasive ductal carcinomas (IDCs) and compared their expression with estrogen receptor (ER), progesterone receptor (PR), and Ki67. CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion. The expression of CgA and CgB was higher in NIDCs than in IDCs: CgA = 70% of NIDC vs 22% of IDC and CgB = 65% of NIDC vs 30% of IDC. There was a statistical correlation between the expression of CgA and PR (p < 0.05) and CgB and ER (p < 0.05) in IDCs without lymph node metastasis. On the other hand, there was a significant correlation between expression of CgB and PR and an inverse correlation between CgA and Ki67 in IDCs of overall cases. The data suggest that CgA and CgB may play some role in the early phase of neoplastic progression.
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PMID:Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma. 1216 59

To better understand the clinical and pathologic features of end-stage, androgen-independent carcinoma of the prostate (CaP), we performed rapid autopsies on 14 men who died of progressive CaP and recorded relevant clinical data. The timing of tumor progression varied widely. The median time to androgen independence was 2 years (range, 4 months to 13.6 years). The median survival after androgen independence was 1 year (range, 1 month to 3.6 years). Because osseous metastases are prevalent in progressive CaP, up to 20 bone sites were systematically sampled in each patient. Bone metastases were widespread; tumor filled the marrow in an average of 14 bone sites. Tumor histology and expression of prostate-specific antigen (PSA) and chromogranin A (CGA) were examined in all metastases and were compared with the primary tumor. Five histological patterns of metastatic tumor were observed: solid (10 patients), macroacinar (1 patient), microacinar (1 patient), clear cell (1 patient), and comedocarcinoma (1 patient). Gleason grade of the primary tumor did not predict the histological pattern of the metastases. Although >70% of tumor cells expressed PSA, the fraction of PSA-positive cells varied widely in separate metastases in some patients (standard deviation >25). Likewise, the fraction of neuroendocrine (NE) (CGA-positive) tumor cells in different metastases varied widely. For example, between 0 and 95% of tumor cells in different metastases in 1 patient had a NE phenotype. The present study highlights the heterogeneity--histologically and immunophenotypically--of metastatic CaP. Consequently, therapy directed to the phenotype of 1 metastasis may have no effect on other metastases in the same patient because of phenotypic heterogeneity.
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PMID:Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. 1287 59

Studies on neuroendocrine differentiation (NED) in conventional gastric adenocarcinomas and its significance on tumor behavior are limited. Our aim was to search for the expression of neuroendocrine differentiation in conventional gastric adenocarcinomas and correlate it with tumor type, stage and expression of VEGF and p53. Forty-two gastrectomy specimens with gastric adenocarcinoma were stained with chromogranin A to detect neuroendocrine differentiation and 45% of the cases were found to be NED (+). No significant correlation was found between NED and tumor type. However, NED was more frequent in advanced stage cases independently of tumor type. VEGF expression was also considerably more frequent in NED (+) tumors compared to NED (-) ones (84% vs. 56%). Moreover, we found a significant correlation between NED and the presence of lymph node metastases. P53 expression in NED (+) tumors was 68%. There was no significant correlation between VEGF and p53 in NED (+) cases. In conclusion, neuroendocrine differentiation is a frequent finding in conventional gastric adenocarcinomas, and although it does not seem to play a specific role in tumor progression, it seems that neuroendocrine cells are one of the factors contributing to angiogenesis by expressing VEGF, especially in advanced stage cases, affecting the incidence of lymph node metastases. Further studies with larger series should be performed to confirm this observation.
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PMID:Neuroendocrine differentiation in gastric adenocarcinomas; correlation with tumor stage and expression of VEGF and p53. 1502 62


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