Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical expression of p53, bcl-2, CD44 standard (CD44S), and the v6 isoform of CD44 (CD44v6) proteins were studied in 14 typical carcinoid tumors (TCs), 11 atypical carcinoids (ACs), and eight small cell carcinomas (SCLCs) in an attempt to use these markers of mutational events and cellular adhesion to discriminate neoplasms demonstrating neuroendocrine differentiation. p53 and bcl-2 overexpression were associated with more aggressive neuroendocrine cell types. p53 nuclear staining was weakly positive in 21% of the TCs, whereas strong nuclear staining was seen in 64% of the ACs and 88% of the SCLCs (P = 0.0047). bcl-2 was present in 21% of the TCs, 91% of the ACs, and 100% of the SCLCs (P = 0.0001). In contrast, CD44S and CD44v6 were inversely correlated with more aggressive types of neuroendocrine tumors. CD44S expression was moderate to strong in all of the TCs and 91% of the ACs but in only 37% of the SCLCs (P = 0.0018). There was no correlation between expression of these markers and tumor size or nodal status, although loss of CD44v6 was associated with lymph node metastases in the TC group only. In the spectrum of neuroendocrine tumors of the lung, p53 and bcl-2 overexpression correlates with more aggressive histologic cell types. The decreasing CD44S expression in AC and SCLC is similar to findings in cancer of the colon and in non-small cell carcinoma of the lung, where loss of CD44S is associated with poor prognosis. In AC and SCLC, but not in cancer of the colon, loss of CD44v6 correlates with more aggressive neoplasms and might correlate with lymph node metastases in TCs.
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PMID:Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung. 873 62

Large cell neuroendocrine carcinoma (LCNEC) of the lung is defined as a poorly differentiated and high-grade neuroendocrine tumor that is morphologically and biologically between atypical carcinoid and small cell lung carcinoma (SCLC). During a survey concerning bcl-2 protein expression in the subtypes of lung cancer, we noticed that two previously diagnosed non-SCLCs met the criteria for LCNEC. Because LCNEC is a newly recognized clinicopathologic entity and because all reported cases have been retrieved from the so-called "neuroendocrine tumor file," we suspected that LCNEC had been underdiagnosed. In the present study, we histologically reviewed 766 surgically resected lung cancers and were able to diagnose 22 (2.87%) LCNECs with the neuroendocrine features subsequently confirmed by immunostaining for multiple neuroendocrine markers. Each case stained positively for at least three general neuroendocrine markers, and 12 (54.5%) also were positive for neuroendocrine hormones. Histologically, most LCNECs showed a marked decrease in or a loss of organoid architecture and could be mistaken for poorly differentiated adenocarcinoma or squamous cell carcinoma. Because our LCNECs are the first to be identified by retrospective review of routinely diagnosed lung cancers, and 18 had been classified as non-SCLC, they may represent cases relatively difficult to diagnose. The present study shows that the most difficult diagnostic factor of LCNEC is the recognition of its light microscopic neuroendocrine features, and LCNEC must be distinguished not only from atypical carcinoid or SCLC, but also from common non-SCLC. Histologically, when an organoid architecture is subtle or absent, the rosettelike structure becomes the best marker for the recognition of neuroendocrine differentiation. Clinically, the prognosis for our LCNECs was significantly worse than that for stage-comparable non-SCLCs (p = 0.046).
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PMID:Large cell neuroendocrine carcinoma of the lung: a histologic and immunohistochemical study of 22 cases. 959 21

Several genetic aberrations have been implicated in the carcinogenesis of small cell lung carcinomas (SCLCs), including tumour suppressor gene p53 deletion and mutation and amplification of the myc family proto-oncogenes. However, their exact ontogeny and carcinogenesis remain unknown. There are no proven aetiological factors for lung carcinoid tumours. Recent evidence suggests that the genetic regulation of apoptosis is of critical importance during tumourigenesis and that oncogene and tumour suppressor genes can regulate the rate, or susceptibility, of cells to undergo apoptosis. In this study, the expression of Bcl-2 protein has been investigated in 77 primary lung neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared with p53 expression. Of the 77 tumours studied, Bcl-2 immunoreactivity was present in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of atypical carcinoid tumours with more than 10 per cent tumour cell positivity. Western and Northern blot analysis revealed that carcinoid tumours expressed the 26 kD protein and bcl-2 transcripts. Whereas 42 per cent of the SCLCs studied displayed p53 protein immunoreactivity in more than 10 per cent of tumour cells, p53 positivity was not found in lung carcinoid tumours. There are statistical differences in Bcl-2 and p53 expression between SCLCs and lung carcinoid tumours. These results suggest that disregulation of the genetic mechanisms controlling apoptosis is a critical step in the progression of SCLC, and the expression of Bcl-2 is involved in the pathogenesis of SCLC and lung carcinoid tumours. The genetic complementation of simultaneously deregulated Bcl-2 and p53 may be implicated in the multistep tumourigenesis of small cell lung cancer.
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PMID:Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. 961 75

Bronchopulmonary well-differentiated neuroendocrine carcinoma (WDNEC) represents a more aggressive neoplasm than does typical carcinoid. Its biological behavior is variable and cannot be predicted on the basis of histopathological features. Nineteen typical carcinoids and 23 WDNECs were studied in order to obtain multiple parameters that should be used in the differential diagnosis between these two lesions and as prognostic markers of WDNEC. Flow-cytometry was performed on paraffin-embedded sections. Mutant p53 protein, the bcl-2 oncoprotein and the Ki-67 antigen were detected by immunohistochemical methods and evaluated quantitatively. WDNEC was more frequently aneuploid than typical carcinoid, had a higher percentage of Ki-67 positive nuclei and presented more frequently the mutant p53 protein. In WDNEC, the mutant p53 (p = 0.001), the bcl-2 oncoprotein (p = 0.002) and the high expression (> or = 16%) of Ki-67 (p = 0.0021) were associated with poor prognosis. The prognostic significance of mutant p53 and bcl-2 oncoprotein could be confirmed by Cox multiple regression survival analysis (p = 0.0005). It seems to be advisable to evaluate these features for the management of the patients affected by WDNEC.
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PMID:Ploidy, proliferative activity, p53 and bcl-2 expression in bronchopulmonary carcinoids: relationship with prognosis. 1044 63

Fifty-three neuroendocrine lung tumors (24 carcinoids, one atypical carcinoid, five large-cell neuroendocrine carcinomas, and 23 small-cell lung carcinomas) were investigated for immunocytochemical expression of several gene products, i.e., p53, Rb, bcl-2, c-kit, mdm-2, cdk-4, p21 proteins, and proliferation index as assessed by MIB-1. The goal of the study was to explore the relationships between histotypes in light of their own gene product-based immunophenotypical profiles. To this aim we applied the multiple correspondence analysis, which is an exploratory statistical multivariate technique that converts a data matrix into a particular type of graphic display in which the rows and columns are depicted as points. Such statistical analysis displayed that some categories of the gene product-based immunophenotyping variables are grouped in the plot identifying three groups: the first group related to carcinoids, the second to small-cell carcinomas, and the third to large-cell neuroendocrine carcinomas. These data support the evidence that carcinoids and small-cell carcinomas are two distinct, apparently immunogenotypically unrelated entities among neuroendocrine lung tumors and that atypical carcinoids and large-cell neuroendocrine carcinomas seem not to represent intermediate steps between them.
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PMID:Gene product immunophenotyping of neuroendocrine lung tumors. No linking evidence between carcinoids and small-cell lung carcinomas suggested by multivariate statistical analysis. 1093 49

Adenocarcinoid of the appendix is a rare tumor with the histological features of both adenocarcinoma and carcinoid tumor. However, its biological behavior and malignant potential are still unclear. We treated two patients with this unusual tumor; a 60-year-old man and a 79-year-old woman. Both patients were initially diagnosed with acute appendicitis followed by an appendectomy. At surgery, the appendix was seen to be acutely inflamed without any macroscopic signs of tumor. Postoperative histological analysis revealed an adenocarcinoid tumor in the appendix, which had spread diffusely into its wall without forming a mass. Immunohistochemical staining with p53, MIB-1, bcl-2, and carcinoembryonic antigen suggested that neither of these tumors were particularly aggressive. Adenocarcinoid of the appendix is a rare tumor, which is very difficult to diagnose preoperatively and even macroscopically, making histological examination essential.
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PMID:Adenocarcinoid of the appendix: report of two cases. 1273 35

Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay in 38 neuroendocrine (NE) lung tumours. A significantly (p = 0.001) different frequency of telomerase positivity was observed among different histological tumour types. Specifically, a positive TRAP signal was observed in 14 of 15 (93%) small cell lung cancers (SCLCs), 7 of 8 (87%) large-cell NE carcinomas (LCNECs), and only 1 of 15 (7%) typical carcinoid tumours. When telomerase activity was correlated with the gene product-based immunophenotypic profile of individual tumours, it was found that the absence of telomerase activity was associated with a lack of bcl-2, p53, and c-kit expression, and characterized by a low proliferation index consistent with the absence of cdk-4 expression and the presence of the cdk inhibitor Rb. Such a phenotype was appreciable in most of the carcinoid tumours. Conversely, telomerase-positive tumours generally showed an immunophenotype consistent with gene product alterations (including high expression of bcl-2, p53, and c-kit, and loss of Rb) and were characterized by a high proliferation index. These telomerase data support the previously reported evidence for two genetically unrelated groups of NE lung tumours (SCLC, and to some extent LCNEC, versus carcinoid tumours) that have distinct phenotypic profiles.
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PMID:Differential expression of telomerase activity in neuroendocrine lung tumours: correlation with gene product immunophenotyping. 1295 25

Carcinoid tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. We examined all aspects of carcinoid tumors including the molecular biology oncogenesis, role of angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit databases were searched using carcinoid as the keyword. English language manuscripts were reviewed and relevant references from a total of 7741 were found. All titles were screened and all the relevant manuscripts were analyzed; we found 307 references pertinent to the history, epidemiology, clinical behavior, pathology, pathophysiology, molecular biology, radiologic imaging, supportive care of carcinoid syndrome, and results of therapeutic clinical trials. Management of patients with carcinoid tumors requires an understanding of the disease process and a multimodality approach. Introduction of long-acting somatostatin analogues has resulted in significant advances in the palliative care of patients with carcinoid syndrome. However, advanced carcinoid tumor remains incurable. Existing therapies for advanced disease have low biologic activity, high toxicity, or both. Clearly, more research is necessary in the areas of molecular biology, targeted therapy, and development of new drugs Future advances in this field need to focus on clinical and biological predictors of outcome. Early works in the area of tumor biology such as the role of p53, bcl-2, bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be explored further.
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PMID:Carcinoid--a comprehensive review. 1469 Jan 53

While the hyperplasia-neoplasia sequence of enterochromaffin-like (ECL) cells has been proposed in the pathogenesis of type I gastric carcinoids, the criteria for distinction between hyperplastic endocrine cell micronest (ECM) and neoplastic ECM have not been established. The aims of this study were to clarify differences between the hyperplasia and neoplasia of ECL cells and determine the optimal classification system for gastric ECL cell proliferations in type A gastritis. Endocrine cell lesions (n=531) from 8 surgically-resected stomachs with type A gastritis were reclassified as either atrophic ECM (n=333), hyperplastic ECM (n=168), neoplastic ECM (all ECM > or =0.1 mm in size, n=15), or typical carcinoid (n=15). Hematoxylin and eosin-stained sections were semiautomatically analyzed by nuclear morphometry. Immunohistochemical expression of bcl-2, p53 and Ki-67 was also investigated. As the histologic grade of histology advanced, the morphometric values of area, circumference and largest diameter of the nuclei significantly increased (p<0.0005), while the frequency of diffuse expression of bcl-2 significantly decreased (p<0.0001). Significant differences were also observed in all morphometric parameters and in bcl-2 positivity between the hyperplastic ECM and neoplastic ECM group. There was no expression of p53 in any of the lesions. The Ki-67 index did not differ between the neoplastic ECM and typical carcinoid groups. These results suggest that our system of classification for gastric endocrine cell proliferations in type A gastritis is appropriate. Nuclear morphometry and bcl-2 immunoexpression are useful parameters for the distinction of neoplastic ECMs from hyperplastic ECMs.
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PMID:Multiple gastric carcinoids and endocrine cell micronests in type A gastritis: Nuclear morphometric and immunohistochemical analysis. 1570 7

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45


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