Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moderately differentiated neuroendocrine carcinoma/atypical carcinoid tumor is the most common nonsquamous malignancy in the larynx; however, due to morphologic overlap and calcitonin immunoreactivity, it can be difficult to distinguish from thyroid medullary carcinoma. Currently, low serum calcitonin is the most reliable means for distinguishing primary laryngeal moderately differentiated neuroendocrine carcinoma from metastatic medullary carcinoma. Thyroid transcription factor-1 (TTF-1) is positive in at least 80% of medullary carcinomas, but has not been evaluated in laryngeal moderately differentiated neuroendocrine carcinomas. Additionally, it has been suggested that p53 is positive in laryngeal moderately differentiated neuroendocrine carcinomas and negative in other neuroendocrine tumors, but this has not been validated. The purpose of this study was to determine if the immunohistochemical markers TTF-1 and p53 could be used to discriminate between laryngeal moderately differentiated neuroendocrine carcinomas and thyroid medullary carcinomas. Eight laryngeal moderately differentiated neuroendocrine carcinomas and 10 thyroid medullary carcinomas were identified from the archival files of the BWH and MGH Pathology Departments. Hematoxylin and eosin slides were reviewed, and immunohistochemistry was performed using antibodies to calcitonin, TTF-1, and p53. Calcitonin immunohistochemistry demonstrated immunoreactivity in 100% of laryngeal moderately differentiated neuroendocrine carcinomas (N=8) and 100% of thyroid medullary carcinomas (N=10). There was weak, focal immunoreactivity with TTF-1 in one of eight (13%) laryngeal moderately differentiated neuroendocrine carcinomas, whereas nine of ten (90%) medullary carcinomas were positive for TTF-1, with strong diffuse staining in seven of these cases (78%). p53 was positive in three of six (50%) laryngeal moderately differentiated neuroendocrine carcinomas, and three of ten (30%) medullary carcinomas. Our data demonstrate that immunoreactivity for TTF-1, but not calcitonin or p53, may be helpful in distinguishing laryngeal moderately differentiated neuroendocrine carcinoma and thyroid medullary carcinoma. In particular, diffuse and/or strong TTF-1 immunoreactivity favors a diagnosis of primary thyroid medullary carcinoma over laryngeal moderately differentiated neuroendocrine carcinoma.
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PMID:Thyroid transcription factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid. 1509 9

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

Factors that determine the clinical course and outcome of patients with gastrointestinal (GI) carcinoid tumors are complex and multifaceted. These include the site of origin within the GI tract, the size of the primary tumor, and the anatomical extent of disease, whether localized, regional, or metastatic to distant sites. The new World Health Organization (WHO) histological classification of endocrine tumors, including carcinoids, represents a significant advance in terms of providing a consistent framework for histopathological interpretation that should facilitate multicenter research on treatment outcomes. Histochemical indicators of a poorer prognosis are the degree of expression of the proliferation protein Ki-67 and the p53 tumor suppressor protein. Adverse clinical indicators are the malignant carcinoid syndrome, carcinoid heart disease, and high concentrations of the tumor markers, urinary 5-HIAA and plasma chromogranin A.
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PMID:Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. 1571 76

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.
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PMID:Endocrine tumours of the stomach. 1625 92

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

Composite adenoma-carcinoid tumors are rare colorectal lesions consisting of intermingled adenomatous and carcinoid components. Unlike other mixed endocrine-glandular colorectal neoplasms, which are generally malignant, their glandular component is histologically benign and their natural history is favorable. We present 4 cases of colonic adenomas containing microcarcinoids, a hitherto undescribed lesion that is either a precursor of composite adenoma-carcinoids or a related but independent entity. The cases, identified among our surgical and consultation files, were endoscopically routine sessile polyps removed from 4 otherwise normal individuals, 3 from the cecum and 1 from the distal colon. The microcarcinoids were 0.5 to 1.5 mm in size and situated within the basal lamina propria, where they interposed between the crypts and muscularis mucosae without disturbing the overall polyp architecture. Histologically, they consisted of collections of low-grade epithelial cells arranged in nests, cords, tubules, and irregular clusters and characterized by eosinophilic, granular, or clear cytoplasm and by round central nuclei with stippled or dusty chromatin. Endocrine differentiation of the microcarcinoids was confirmed by the expression of 3 or more of the following: Grimelius argyrophil, chromogranin, synaptophysin, neuron-specific enolase and somatostatin. No mitotic figures or MIB-1 or p53 positivity were observed. The glandular component of the polyps was unremarkable in 3 cases, but 1 polyp, in addition to a microcarcinoid, showed a diffuse pattern of mixed adenomatous-endocrine differentiation. The patients' clinical course was benign on the basis of 2 years' median follow-up (range, 6 mo to 10 y). Two patients with incomplete polypectomies underwent hemicolectomy revealing no residual endocrine neoplasia. Awareness of microcarcinoids in colonic adenomas should help avert potential diagnostic pitfalls posed by their pleomorphism, basal location, and infiltrative patterns, and may help clarify their natural history and possible relationship to composite glandular-carcinoid tumors.
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PMID:Microcarcinoids in large intestinal adenomas. 1712 8

Carcinoid and islet-cell carcinoma are often also known as low-grade neuroendocrine carcinomas. They are often slow-growing but can be resistant to standard therapy. While somatostatin analogues are often used to control hormonal syndromes, there is currently no therapy approved in the US for control of carcinoid tumor growth. For islet-cell carcinoma, streptozocin-based chemotherapy may induce tumor shrinkage, but second-line option are limited. This chapter reviews the molecular biology of neuroendocrine tumors, including the roles of MENIN, TSC2, NF-1, vHL, p53, bcl-2, bax, VEGF, IGF, PDGF, EGFR, and mTOR. Recently, there has been interest in developing molecularly targeted therapy for this group of diseases. Phase-II studies with imatinib, bevacizumab, sunitinib, gefitnib, temsirolimus, and everolimus (RAD001) have completed accrual. Encouraging results have been observed in studies with VEGF and mTOR inhibitors. Phase-III study of bevacizumab is planned in the US. Large-scale multinational phase-II and -III studies of everolimus are under way.
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PMID:Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma. 1738 71

Here, we report the case of patient with multiple gastric carcinoids showing histopathological behavior similar to that of type I carcinoid tumors of the stomach. The patient was a 61-year-old man diagnosed as having a gastric tumor, which was revealed by follow-up computed tomography. Upper gastrointestinal endoscopy revealed a protruded tumor in the greater curvature and a small polyp in the anterior wall of the upper stomach. A biopsy revealed gastric carcinoid. Because he refused to be operated for gastric carcinoid, upper gastrointestinal endoscopy was performed 5 months later. A malignant transformation of the gastric carcinoid was strongly suspected. Therefore, the patient was admitted for operation. Laboratory findings were normal. With the diagnosis of type III gastric carcinoid, total gastrectomy was performed. Microscopic examination revealed that the carcinoid tumor was confined to the submucosa and that the small polyp mentioned earlier was also a carcinoid. Microcarcinoids and numerous enterochromaffin-like cell hyperplasias were observed along the muscularis propria of the fundus. The tumor differed from typical type I gastric carcinoids in several ways. Immunohistochemical staining for chromogranin A, synaptophysin, and cytokeratin was positive. However, p53 was absent, and the MIB-1 index was low. Two years after surgery, the patient is alive without recurrence.
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PMID:A case of multiple gastric carcinoids that could not be preoperatively diagnosed. 1808 38

Neuroendocrine tumours are the second most common laryngeal neoplasms, following squamous carcinoma. In this paper, we report the case of a moderately differentiated neuroendocrine carcinoma NEC (atypical carcinoid) of the larynx in a heavy smoker 67-year-old woman, with a history of hoarseness, dysphagia and dyspnea. The lesion was biopsied and microscopic examination revealed moderately differentiated NEC; thus the patient underwent supraglottic laryngectomy with lymphadenectomy. Here, we emphasized the morphological criteria for a correct pathological diagnosis. Moreover, because it has been demonstrated that many neuroendocrine neoplasms and malignant lesions of the larynx can be related to human papilloma virus (HPV), for the first time, we probed to verify if laryngeal neuroendocrine carcinoma could be due to an HPV infection by using polymerase chain reaction amplification (PCR) of tumoural DNA. On immunohistochemical analysis, the lesion characteristically revealed both neuroendocrine and epithelial differentiation with diffuse staining for chromogranin A, synaptophysin and neuron-specific enolase (NSE) and epithelial membrane antigen (EMA) and overexpression of p53 protein. PCR of NEC DNA did not show any signal for HPV DNA. Thus, this neoplasm is not due to an HPV infection, but a mutation of p53 gene which could cause immunohistochemical overexpression of p53 protein.
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PMID:Primary moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the larynx: A case report with immunohistochemical and molecular study. 1861 41

Appendiceal tumors exhibiting both neuroendocrine and glandular differentiation are uncommon and have caused difficulty in pathologic classification, prediction of prognosis, and clinical management. Previously, such lesions have been variously designated as adenocarcinoid, goblet cell carcinoid (GCC), and mixed adenocarcinoma carcinoid. In this study, we undertook a retrospective investigation of 63 such cases and classified them as typical GCC (group A) and adenocarcinoma ex GCC on the basis of the histologic features of the tumor at the primary site. The adenocarcinoma ex GCC group was further divided into signet ring cell type (group B) and poorly differentiated adenocarcinoma type (group C). The clinical characteristics and prognosis were compared within these groups and with conventional de novo appendiceal adenocarcinomas. Both groups A and B tumors shared a similar immunoprofile, which included generally focal immunoreactivity for neuroendocrine markers, and a normal intestinal type mucin glycoprotein profile (negative MUC1 expression and preserved MUC2 immunoreactivity). The proliferative index was relatively low in these tumors and slightly increased from groups A to B tumors (11% to 16%). Both beta-catenin and E-cadherin exhibited a normal membranous staining pattern in groups A and B tumors. The poorly differentiated adenocarcinomas ex GCC (group C) demonstrated abnormal p53 and beta-catenin immunoreactivity. The mean follow-up time was 49+/-5 (SE) months. The overall disease-specific survival for all subtypes was 77%, with 46% of patients without evidence of disease and 31% alive with disease. The mean survival was 43+/-7 months. All the patients with clinical stage of I or IIA disease had a favorable outcome after appropriate surgery with or without chemotherapy. Although most patients (63%) with GCC presented at an advanced clinical stage, their clinical outcome could be differentiated by subclassification of tumors. The stage IV-matched 5-year survival was 100%, 38%, and 0% for groups A, B, and C, respectively. In conclusion, GCC is a distinctive appendiceal neoplasm that exhibits unique pathologic features and clinical behavior. They display a spectrum of histologic features and possess the potential to transform to an adenocarcinoma phenotype of either signet ring cell or poorly differentiated adenocarcinoma types. Careful evaluation of the morphologic features of GCCs and appropriate pathologic classification are crucial for clinical management and prediction of outcome. Surgical management with right hemicolectomy is recommended after appendectomy for most cases, particularly those with an adenocarcinoma component (groups B and C).
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PMID:Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. 1947 Nov 56


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