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)

Foamy gland adenocarcinoma is a variant of pancreatic ductal carcinoma, whose precursor has not been described. We describe here the morphologic and immunohistochemical features of the pancreatic intraepithelial neoplasia (PanIN) lesions associated with invasive foamy pancreatic adenocarcinoma. The staining properties and morphologic and immunohistochemical features of 3 foamy PanIN lesions were compared with those of 7 pancreatic foamy gland adenocarcinomas. Hematoxylin and eosin, Mayer mucicarmine, periodic acid-Schiff, and Alcian blue stains were available for review in all cases. Immunohistochemical labeling for cytokeratin (CK)7, CK20, carcinoembryonic antigen polyclonal, MUC1, MUC2, CDX2, p53, and cyclin D1 was performed. The PanIN-1 lesions were found in the nonneoplastic pancreas and were similar to the PanIN-1 lesions of ordinary pancreatic ductal carcinoma. The PanIN-2 and -3 lesions were recognized immediately adjacent to or within the invasive foamy gland carcinoma. In these lesions, small or markedly dilated ducts were lined by cuboidal and columnar dysplastic nonfoamy cells and foamy cells. Hobnail cells were present in 2 cases. The PanIN-1, 2, and 3 lesions and the invasive foamy gland adenocarcinomas stained with mucicarmine, periodic acid-Schiff, and Alcian blue. The 3 PanIN-2 and -3 lesions and all 7 invasive foamy adenocarcinomas labeled with CK7, carcinoembryonic antigen polyclonal, and MUC1, whereas only 2 PanIN-2 and -3 lesions and 5 invasive adenocarcinomas showed immunoreactivity for cyclin D1 and p53. Three distinctive foamy PanIN lesions were identified within 7 invasive foamy gland pancreatic adenocarcinomas. The gradual progression of cytological and architectural abnormalities of the PanIN lesions from PanIN-1 to PanIN-3 excludes neoplastic ductal spread. These foamy PanIN lesions probably represent cancer precursors.
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PMID:The foamy variant of pancreatic intraepithelial neoplasia. 1862 Sep 91

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

We describe a rare case of esophageal polypoid dysplasia with gastric phenotype and focal intramucosal carcinoma associated with Barrett's esophagus. A 69-year-old man with a long history of gastroesophageal reflux disease was initially seen at an outside institution for evaluation of significant dysphagia. Screening upper gastrointestinal endoscopic evaluation revealed a large intraluminal polypoid lesion occluding the distal portion of the esophagus. Surgery was performed with resection of the distal esophagus and proximal stomach. The histopathologic examination of this lesion revealed an exuberant polypoid gastric epithelium with areas of low-grade dysplasia, high-grade dysplasia, and focal intramucosal carcinoma. A few residual foci of specialized intestinal metaplasia consistent with Barrett's esophagus without dysplasia were identified at the proximal and distal ends of the lesion. Immunohistochemically, this lesion revealed a pattern of expression of apomucins (MUC5AC diffusely positive, MUC1 and MUC6 focally positive, and MUC2 negative) consistent with a gastric foveolar phenotype. In addition, in the dysplastic areas, there was high Ki-67 labeling index and no overexpression of p53 protein. In our opinion, this case represents a precursor lesion of an extremely well-differentiated adenocarcinoma of gastric foveolar phenotype that has been previously documented in the stomach and in the duodenum and that now for the first time we report in the esophagus in association with Barrett's intestinal metaplasia.
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PMID:Esophageal polypoid dysplasia of gastric foveolar phenotype with focal intramucosal carcinoma associated with Barrett's esophagus. 1872 40

The author reports herein two cases of ductal adenoma of the breast with an emphasis on immunohistochemistry. Both cases (patient 1, 58-year-old woman; patient 2, 78-year-old woman) were clinically suspected as carcinoma, and core biopsies were 'indeterminate' or 'suspicious for malignancy'. Excisional biopsy and wide excision were performed. Histologically, both cases were ductal adenomas composed of ductal epithelial cells and myoepithelial cells. Patient 1 had extensive apocrine metaplasia. Immunohistochemically, myoepithelial cells were noted in both cases; cytokeratin (CK) 14 and p63 were the most reliable myoepithelial markers, followed by CD10, alpha-smooth muscle actin and S100 protein. CK profile was as follows: positive expression of CK5/6, CK18, CK19, and high-molecular-weight CK, and negative expression of CK20. This CK profile was the same as that of non-tumorous ducts, suggesting that the CK profile does not alter in tumorigenesis. The tumor cells expressed p53 protein (case 1, positive cell percentage 5%; case 2, 7%), c-erbB2 (HER2/neu, 76%, 64%), CEA (5%, 0%), estrogen receptor (33%, 84%), but were negative for progesterone receptor. Ki-67 labeling was 5% and 3%, respectively. MUC apomucin expression was as follows: MUC1, 92%, 100%; MUC2, 0%, 0%; MUC5AC, 0%, 0%; and MUC6, 5%, 0%. Non-tumorous ducts expressed MUC1, but were negative for MUC2, MUC5AC and MUC6.
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PMID:Ductal adenoma of the breast: immunohistochemistry of two cases. 1906 57

Carcinoma arising from Rokitansky-Aschoff sinus (RAS) is extremely rare; only eight cases have been reported in the literature. Herein is reported a case of minute adenocarcinoma arising in RAS. A 77-year-old Japanese man with gallbladder stones underwent cholecystectomy. A tiny submucosal tumor (1 cmx1 cm) was incidentally recognized. Histologically, the submucosal tumor was located in the subserosa and, to a lesser extent, in the fibromuscular layer. It was adenocarcinoma. RAS were recognized within the tumor, and there was a gradual transition between RAS and the adenocarcinoma. Mucin histochemistry indicated neutral and acidic mucins in the cytoplasm and lumens of the adenocarcinoma cells. Immunohistochemistry showed that the adenocarcinoma cells were positive for cytokeratin, epithelial membrane antigen, carbohydrate antigen 19-9, K-i67 (labeling=80%), MUC1, MUC5AC and MUC6. In contrast, the adenocarcinoma cells were negative for CEA, c-erbB2, p53 protein, MUC2 and CD10. In summary, minute subserosal adenocarcinoma, which arose in RAS, was found incidentally; therefore careful examination of resected gallbladders is necessary.
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PMID:Gallbladder adenocarcinoma arising in Rokitansky-Aschoff sinus. 1906 58

Presented herein is an unusual case of intraductal tubular carcinoma, intestinal type, of the pancreas. This tumor was characterized by intraductal adenoma with a few malignant foci, and also by entire involvement of the main pancreatic duct and no involvement of its branches. A 67-year-old man was admitted to hospital because of abdominal pain. On endoscopy and endoscopic retrograde cholangiopancreatography, irregular pancreatic duct was seen. No mucus secretion was observed on endoscopy. Because a biopsy showed tubular atypical cells, pancreato-duodenectomy was performed. Grossly, the entire main pancreatic duct had intraductal tumor, sparing its branches. No intraductal mucus was noted. Microscopically, the entire main pancreatic duct had proliferation of tubular adenomatous tumor without secretory mucins. Goblet cells were present in some areas. No pyloric type tubules were recognized. Malignant transformation was present in a few areas. No invasive features were recognized. On mucin histochemistry the tumor cell cytoplasm contained a little or no neutral and acidic mucus, and no secretory mucins were recognized. Immunohistochemically, the tumor cells were positive for cytokeratins (CK), CK 8, 9, 18, 19 and 20, epithelial membrane antigen, CDX2, carbohydrate antigen 19-9, and Ki-67 (labeling 30%), MUC2, MUC5AC and MUC6, and CD10. The tumor cells were negative for C-erbB2, MUC1, trypsin, pancreatic amylase and pancreatic lipase. The tumor cells were negative for p53 protein, but the malignant foci were positive for p53 protein and had high Ki-67 antigen (labeling 60%). The patient was free of disease 4 years after the operation. In summary, presented here is an extremely rare case of intraductal tubular carcinoma, intestinal type, showing focal malignant foci.
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PMID:Intraductal tubular carcinoma, intestinal type, of the pancreas. 1912 Oct 93

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Prognostic biomarkers are lacking, and treatment has limited effect on survival. Tissues from Surveillance, Epidemiology, and End Results registries (Iowa, Hawaii, and Los Angeles) were used to build a tissue microarray of 161 pancreatic tumors (113 resections and 48 biopsies). Proportional hazard models adjusted for age, race, sex, stage, time-period of diagnosis, and treatment. Associations were examined between markers (MUC1, MUC2, MUC5AC, synaptophysin, chromogranin, neuron specific enolase, epidermal growth factor receptor, HER2, CD5, CD138, CK5/6, CK19, CK20, and p53) and survival time from diagnosis. After adjusting for covariates, borderline statistically significant associations were seen between expression of each of the three mucins (MUC1, MUC2, and MUC5AC) and shorter survival time. The associations strengthened for 154 (96%) adenocarcinomas, particularly the 120 (75%) well-differentiated to moderately differentiated ductal adenocarcinomas, a tumor type that occurred more often in the cohort among White cases than cases of other racial origin (P<0.01). For differentiated ductal adenocarcinomas, associations with shorter survival time were seen for expression of all three mucins combined versus other mucin expression patterns (adjusted hazard ratio, 1.8; 95% confidence interval, 1.2-2.6) and for MUC2(+) versus MUC2(-) expression (adjusted hazard ratio, 1.6; 95% confidence interval, 1.1-2.4). Mucin gene expression, particularly MUC2 expression, may have prognostic value for differentiated adenocarcinomas. Tumor histologies differed in this and Japanese cohorts. The tissue microarray is available to evaluate other biomarkers. Tissue-based surveillance can be used to monitor tumor histology in populations and facilitate applied research.
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PMID:Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray. 1927 52

We have encountered cases of unusual intraductal pancreatic neoplasms with predominant tubulopapillary growth. We collected data on 10 similar cases of "intraductal tubulopapillary neoplasms (ITPNs)" and analyzed their clinicopathologic and molecular features. Tumor specimens were obtained from 5 men and 5 women with a mean age of 58 years. ITPNs were solid and nodular tumors obstructing dilated pancreatic ducts and did not contain any visible mucin. The tumor cells formed tubulopapillae and contained little cytoplasmic mucin. The tumors exhibited uniform high-grade atypia. Necrotic foci were frequently observed, and invasion was observed in some cases. The ITPNs were immunohistochemically positive for cytokeratin 7 and/or cytokeratin 19 and negative for trypsin, MUC2, MUC5AC, and fascin. Molecular studies revealed abnormal expressions of TP53 and SMAD4 in 1 case, but aberrant expression of beta-catenin was not observed. No mutations in KRAS and BRAF were observed in the 8 cases that were examined. Eight patients are alive without recurrence, 1 patient died of liver metastases, and 1 patient is alive but had a recurrence and underwent additional pancreatectomy. The mitotic count and Ki-67 labeling index were significantly associated with invasion. All the features of ITPN were distinct from those of other known intraductal pancreatic neoplasms, including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and the intraductal variant of acinar cell carcinoma. Intraductal tubular carcinomas showed several features that were similar to those of ITPN, except for the tubulopapillary growth pattern. In conclusion, ITPNs can be considered to represent a new disease entity encompassing intraductal tubular carcinoma as a morphologic variant.
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PMID:Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. 1944 Jan 45

Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (P<0.05), including beta-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-kappaB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (P<0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (P<0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (P<0.05, both). NF-kappaB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also beta-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-kappaB positivity, and beta-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.
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PMID:Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors. 1944 92

Adenocarcinoma of the lower esophagus and esophagogastric junction is increasing in incidence in Western countries. A metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is established. Two patterns of Barrett dysplasias have been described-adenomatous (type 1) and non-adenomatous (type 2 or foveolar/hyperplastic type). Interestingly, little is known about non-adenomatous dysplasia. Esophagogastrectomy cases from 41 patients with glandular dysplasia with and without associated invasive adenocarcinoma of the lower esophagus were evaluated for expression of MUC2, MUC5AC, CDX2, villin, Ki67 and p53. Results were correlated with sub-classification of the dysplasia into morphologic patterns of adenomatous vs foveolar vs hybrid type. In addition, clinicopathological parameters including the presence and extent of background intestinal metaplasia were also evaluated. Foveolar type dysplasia was present in 46% of the cases and thus, was more common than adenomatous type or hybrid type (both approximately 27%) dysplasia. Immunohistochemistry confirmed the histological stratification in all cases. Foveolar type dysplasia commonly expressed MUC5AC (P<0.12) but was consistently negative for markers of intestinal differentiation, MUC2, CDX2 and villin (all P<0.01). By contrast, adenomatous type dysplasia frequently displayed intestinal differentiation markers (all P<0.0001) Hybrid-type dysplasia was similar to adenomatous type dysplasia in showing expression of intestinal differentiation markers (P<0.01) and therefore could not be sustained as a separate category. In conclusion, our study provides evidence for a non intestinal pathway to neoplastic development in Barrett esophagus, that is, gastric metaplasia-foveolar dysplasia-adenocarcinoma.
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PMID:Foveolar type dysplasia in Barrett esophagus. 2022 80


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