Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Routinely processed normal, hyperplastic and neoplastic prostatic tissue was immunohistochemically investigated with antibodies against chromogranin A and B and secretogranin II. In normal and hyperplastic prostates all three peptides were immunolocalized in scattered neuroendocrine cells situated within the glandular epithelium. In 17 prostatic carcinomas with pronounced neuroendocrine differentiation and in a case of prostatic carcinoid, chromogranin B was the major component whereas chromogranin A and secretogranin II were virtually absent in poorly differentiated (grade III) tumours. Neuroendocrine differentiation in prostatic cancer is most likely to be associated with a poor clinical outcome; thus, chromogranin B appears to be a useful marker in the histopathological diagnosis of these neoplasms.
 ...
PMID:Immunohistochemical localization of chromogranins A and B and secretogranin II in normal, hyperplastic and neoplastic prostate. 751 71

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has potential prognostic and therapeutic implications. In a recent study we were able to provide immunohistochemical evidence that endocrine-paracrine cell types represent an androgen-insensitive cell population in prostate cancer, documented by the consistent lack of the pertinent receptor. In this study we investigated the proliferative activity of endocrine-paracrine cell types in normal, hyperplastic, and neoplastic prostate tissue. Using double-label techniques for the endocrine marker chromogranin A (chr A) and the proliferation-associated MIB-1 antigen, we evaluated the proliferative status of endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma showing marked NE differentiation. In this series of carcinomas and in nonneoplastic tissue the proliferative activities were exclusively restricted to nonendocrine cell populations, whereas endocrine-paracrine cell types characterized by Chr A consistently lack MIB-1 immunoreactivity. This may indicate that prostatic endocrine-paracrine cell types do not participate in the cell cycle during normal, hyperplastic, and neoplastic prostatic growth. Based on the present information, the endocrine phenotype can be considered to be an androgen-insensitive, postmitotic subpopulation in the prostate and prostate cancer.
 ...
PMID:Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. 852 16

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.
 ...
PMID:The prognostic influence of neuroendocrine cells in prostate cancer: results of a long-term follow-up study with patients treated by radical prostatectomy. 754 77

Neuroendocrine differentiation is a frequent occurrence in common prostatic adenocarcinomas and may have prognostic implications in prostatic malignancies. In the present study, we used immunohistochemical double label methods to evaluate the nuclear androgen receptor (AR) status in endocrine-paracrine (EP) cells of normal, hyperplastic, and neoplastic prostate including tumours that recurred after hormonal and radiation therapy. In normal and hyperplastic glands, EP cells characterized by the panendocrine marker chromogranin A (Chr A) did not reveal AR-positivity. This may indicate that prostatic EP cells represent an androgen-independent cell population whose regulatory functions are not influenced by circulating androgens. Unequivocal co-expression of Chr A and AR was very rarely detected in subsets of endocrine differentiated tumour cells in treated and untreated specimens. The widespread absence of nuclear AR in neuroendocrine tumour cells suggests that this phenotype belongs to those cell clones in prostate cancer which are initially androgen-independent and refractory to hormonal therapy.
 ...
PMID:Androgen receptor status in endocrine-paracrine cell types of the normal, hyperplastic, and neoplastic human prostate. 769 24

Prostate cancer with marked neuroendocrine (NE) differentiation belongs to the hormone resistant carcinomas. We report the development of TSH-secreting small cell prostate cancer (SCPC) from high grade adenocarcinoma (Gleason score 8) with an elevated number of chromogranin A positive cells located in benign structures adjacent to the cancer. Conversion to SCPC was followed-up during 4 years. The initial adenocarcinoma exerted a stronger positivity for PAP than for PSA (respective staining indexes, Sls, 2.2 and 1.8, maximum staining 3.0). In the developed SCPC, 2 cell subpopulations that were derived from epithelial cells were found (positive stain for EMA and CEA, respectively) and from one of them originated CEA-positive liver metastases. Blood CEA and NSE levels were elevated in SCPC (284 ng/ml and 24.5 ng/ml). However, blood TPS level which reflects proliferation of epithelial cells was within the normal range. The development of a << pure >> sarcomatoid prostatic tumor from adenocarcinoma with 2 areas of similar differentiation grades (Gleason score 7 and 9-10) that initially differ in staining for PSA and PAP (SIs for PSA were 1.2 and 0.02 and for PAP were 1.6 and 0.02, respectively) was followed-up during 4 years of treatment with Estracyt. Adenocarcinoma tissue specimens was slightly CEA-positive. The disappearance of lower grade adenocarcinoma during treatment was accompanied by the development of sarcomatoid areas that were 100% vimentin positive. In the last year of follow-up the primary tumor was composed only of vimentin positive sarcomatoid cells with a slight positivity for Chromogranin A, NSE and ACTH. In parallel, normal serum PSA and PAP values and elevated CEA and NSE serotests (12.6 ng/ml and 24.7 ng/ml, respectively) were found. Blood TPS level was at the upper limit of the normal range. Scintigraphy revealed extensive liver metastases. The recorded data indicate (i) extremely poor prognoses associated with high grade adenocarcinomas that demonstrate stronger immunohistochemical positivity for PAP than that for PSA (ii), chromogranin A positive cells in benign structures adjacent to the cancer as a possible paracrine promoter of SCPC from poorly differentiated adenocarcinoma, and (iii) a high degree of heterogeneity of both SCPC and sarcomatoid prostatic neoplasms with some evidence for definite links (EMA and CEA) to secretory epithelial cells.
 ...
PMID:Immunohistochemical staining and serotest markers during development of a sarcomatoid and small cell prostate tumor. 784 May 15

Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.
 ...
PMID:Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. 820 89

It is controversial whether neuroendocrine (NE) differentiation in adenocarcinoma of the prostate is associated with more aggressive behavior. Most studies included patients with tumors of a wide range of grades and stages and an end point of disease-specific survival, a relatively insensitive marker of progression. The authors studied completely embedded radical prostatectomy specimens from 104 patients with clinically organ-confined carcinoma and no history of adjuvant or neoadjuvant therapy. Progression was marked by a serum prostate-specific antigen (PSA) concentration greater than or equal to 0.2 ng/mL. Seventy-six men did not progress, with a mean follow-up period of 8.0 years (range = 7 to 10 years). Forty-eight men progressed at a mean time after surgery of 3.6 years (range = 1 to 8 years). Twenty-one percent of the tumors were organ confined: 79% had capsular penetration. Seminal vesicles and lymph nodes were negative in all cases. A representative section through the main tumor mass was stained for chromogranin A. Reactive neoplastic cells were counted subjectively as well as individually enumerated. Gleason grade, pathological stage, and degree of NE differentiation all correlated with progression. Only grade and extent of NE differentiation predicted progression in a multivariate analysis. NE differentiation did not correlate with stage or grade. Extent of NE differentiation separated patients (59 cases) with tumors of Gleason sum less than or equal to 6 into groups with high and low risks for progression (P < .008) independent of Gleason sum. Extent of NE differentiation provides prognostic information in addition to that provided by grade in cases of early prostate cancer treated by radical prostatectomy.
 ...
PMID:Neuroendocrine differentiation in prostate cancer: enhanced prediction of progression after radical prostatectomy. 869 12

Neuroendocrine (NE) cells can be identified in benign and malignant prostatic epithelia. Factors regulating their presence and their functions are poorly understood, mainly due to a lack of suitable experimental models. Fifteen in vitro and in vivo prostatic cancer tumor models, including a number of newly established in vivo models, were studied immunohistochemically for the presence of NE cells under different hormonal conditions. None of the in vitro models (PC-3, DU 145, LNCaP, and TSU) contained NE cells. Five of the seven xenograft models established at this laboratory contained NE cells. In three of these, NE cells were found only in the initial mouse passages. In the other two (PC-295 and PC-310), the NE phenotype was stable. NE features were confirmed by transmission electron microscopy and by Western analysis of chromogranin A expression. Immunohistochemical double-labeling experiments confirmed that NE cells in prostate cancer are post-mitotic (no Ki-67 expression) and do not express the androgen receptor. In the PC-295 and PC-310 models, short-term androgen withdrawal resulted in a rapidly increased number of NE cells. A time course experiment with PC-295-bearing mice strongly suggests that this increase occurred by induction of NE differentiation rather than by rapid proliferation and subsequent differentiation or selective persistence. In conclusion, these models are suitable to resolve fundamental questions with regard to the presence and functions of NE cells in human prostate cancer.
 ...
PMID:Neuroendocrine differentiation in human prostatic tumor models. 878 Mar 90

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter-beta-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.
 ...
PMID:Androgen-repressed phenotype in human prostate cancer. 898 79

Breast cancer is the most frequent malignant tumor in women, whereas it is rare in men. In our own case series the ratio is 175:1. The present paper deals with an evaluation of clinical and morphological findings from a series of 54 de novo male breast cancers observed in our institution from 1978 to 1996 and a comparative discussion of 528 female breast cancers from the same geographic area. We should like to focus on the following observations: At the time of histopathological diagnosis, male patients with breast cancer were on average 67 (34-87) years old and thus 5 years older than women. Below the age of 40, breast cancer is very rare in men. The lag time between first symptoms and surgery was on average 42 weeks, i.e. twice as long as in women. In the vast majority of cases palpation of a retromamillary nodule was the leading diagnostic symptom. Mamillary secretion appeared to be an early symptom with favorable relation to prognosis by tumor size whereas diffuse breast swelling was an unfavorable late symptom. Bilateral carcinoma and double cancer (breast and prostatic cancer) was observed in one case each. Three patients (3/51 = 6%) had a positive family history (breast cancer in 1st and 2nd degree relatives). The average invasive tumor size was nearly identical with 23 mm (s11.02) in men and 25 mm (s13.48) in women. Men presented more frequently with regional lymph node metastases (53% versus 45%), which tended to develop earlier. pT4 cancers were twice as frequent in men compared to women. In situ cancers were found in 2% (1/54) in men and 4% in women. Similar to females, male breast cancers are predominantly of ductal histological type (NOS-cancers), classical lobular carcinoma with LCIS-components were not observed; special forms (tubular, papillary, mucinous) are slightly more common in men. When reviewing our series, need for revision of the origin of tumor was not found in any of the cases. Metastases of prostatic cancer were never misinterpreted as primary breast cancer. In case of isolated NSE-reaction, cancers with carinoid differentiation pattern are to be found in nearly every second tumor. However, when multiple markers were used (chromogranin A or synaptophysin) only 10% displayed such pattern, which corresponded to a positive hormone receptor status in each case. Quantitative (enzyme immunoassay) and semiquantitative (immunohistochemistry) analysis of steroid hormone receptor status was positive in 86% of 35 cases in men and in 75% in women. In contrast to female breast cancer, hormone status proved to be independent of age in males. The average levels of estrogen and progesterone were higher in men. Overlapping results were found only when cases were compared with postmenopausal women. The Nottingham prognostic index, a product of primary tumor size, axillary lymph node status and grading allows an approximative estimate of the course of the disease; its predictive value is higher than that of isolated tumor markers.
 ...
PMID:[Breast carcinoma in the man. Current results from the viewpoint of clinic and pathology]. 915 4


1 2 3 4 5 6 7 8 9 10 Next >>