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)

Barrett's oesophagus is a premalignant condition that predisposes to the development of oesophageal adenocarcinoma. It is detected on endoscopy and confirmed histologically by the presence in the lower oesophagus of a metaplastic mucosa, the so-called specialised epithelium, which resembles incomplete intestinal metaplasia in the stomach. These similarities with incomplete intestinal metaplasia are present on histology, mucin histochemistry, and immunohistochemistry with various differentiation markers (cytokeratins and MUC antigens). On morphology, the carcinogenetic process of Barrett's mucosa progresses through increasing grades of epithelial dysplasia. Dysplasia, a synonym of intraepithelial neoplasia, is the only marker that can be used at the present time to delineate a population of patients at high risk of cancer. Among the numerous molecular events that have been shown to play a role in the neoplastic transformation of Barrett's mucosa, only changes in DNA ploidy, increased proliferation, and alterations of the p53 gene have been suggested to be of potential help in the surveillance of patients.
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PMID:Barrett's oesophagus: from metaplasia to dysplasia and cancer. 1571 Oct 8

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.
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PMID:Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses. 1576 89

We report 2 previously undescribed morphological variants of pancreatic intraepithelial neoplasia (PanIN). The first variant with an intestinal phenotype was associated with mucinous carcinomas that occurred in the tail of the pancreas of 2 men (60 and 65 years old). The carcinomas lacked the characteristic ovarian-like stroma of mucinous cystic neoplasms observed in female patients and did not show a papillary architecture. Whether they represent mucinous cystadenocarcinomas or mucinous carcinomas that arose from the flat variant of intraductal papillary mucinous neoplasms could not be determined with certainty. Microscopically, the intestinal type of PanIN was composed of pseudostratified columnar cells similar to those of colonic adenomas and showing variable degrees of dysplasia. A significant increase in the MIB-1 labeling index correlated with the severity of dysplasia. In contrast to conventional PanIN, the intestinal variant expressed MUC-2 and was MUC-1 negative. The second type of PanIN had an oncocytic phenotype, coexpressed MUC-2 and MUC-1 mucins, and was associated with intraductal oncocytic papillary carcinomas that showed a similar immunohistochemical mucin profile. Both intestinal and oncocytic types of PanIN expressed DPC4 and lacked p53 reactivity. The anatomical separation of the PanINs from the carcinomas and the gradual progression of cytological and architectural abnormalities in both variants of PanIN argue against ductal spread (cancerization of the ducts). The intestinal and oncocytic variants of PanIN broaden the morphological spectrum of this intraductal lesion. Although their significance is unknown, the possibility that these PanIN variants represent cancer precursors should be considered.
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PMID:Intestinal and oncocytic variants of pancreatic intraepithelial neoplasia. A morphological and immunohistochemical study. 1580 12

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.
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PMID:Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases. 1583 84

We report on a case of mucinous carcinoma of the thyroid in an 82-year-old Japanese woman. The 3 x 2 x 2-cm thyroid tumor located in the patient's right lateral lobe was soft and yellowish gray on the cut section. Microscopically, the tumor was composed entirely of strands or solid clusters accompanied by extensive extracellular mucin. Extracellular mucin was positive with Alcian blue stain and negative with periodic acid-Schiff stain. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid-specific transcription factor 1, and low-molecular-weight cytokeratin but negative for carcinoembryonic antigen, calcitonin, and high-molecular-weight cytokeratin. The MIB-1 labeling index was rather high (11%), and immunoexpression of p53 was detectable in the nuclei of carcinoma cells. From these findings, we classified the present tumor as a mucinous carcinoma of the thyroid (poorly differentiated thyroid carcinoma producing massive extracellular mucin). The patient died of multiple metastases 4 years after the initial operation.
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PMID:Mucinous carcinoma (poorly differentiated carcinoma with extensive extracellular mucin deposition) of the thyroid: a case report with immunohistochemical studies. 1602 78

Mucin core proteins are known to be present in various organs and are specifically expressed with carcinogenesis and closely associated with the prognoses of various malignant tumors in the digestive tract such as colorectal cancer. The present study evaluated correlations between mucin and p53 expression and prognosis of gallbladder cancer using surgically resected tissue specimens from 26 patients with gallbladder carcinoma surgically treated at our hospital. Immunohistochemical staining was performed using MUC 1, MUC2, and p53 monoclonal antibody. The level of antigen expression in the lesion was classified into four stages: none(-), slight(+), moderate (++), and severe (+ + +). According to the UICC classification, histopathological grading, levels of T, N, and M factors, and tumor stages were compared with regard to the correlations with mucin and p53 expression. All cases were classified into two groups according to the results of mucin immunohistochemistry: group A (MUC1, > or = ++; and MUC2, < or = +) and group B (MUC1, < ++; or MUC2, > +). Postoperative survival periods were compared between the two groups and p53-positive and -negative groups. Neither histological grading nor T factor correlated with mucin or p53 expression, respectively. Moreover, neither N factor nor M factor correlated with mucin or p53 expression. Furthermore, stage grouping did not correlate with mucin or p53 expression. However, when the correlation between the postoperative survival period and mucin expression was evaluated, the mean postoperative surgical period was significantly shorter in Group A than in Group B (1.02 years in Group A vs 2.92 years in Group B; P = 0.016). There was no relationship between postoperative survival period and p53 positivity. Mucin expression was independent of various tumor growth factors and clearly reflected the prognosis of gallbladder cancer. Because the relative malignancy of gallbladder cancer could be evaluated by examining the level of glycoprotein expression in tumor tissue, mucin could be a more important marker than p53 for predicting prognosis in gallbladder carcinoma using surgically resected tissue specimens.
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PMID:Prediction of prognosis in gallbladder carcinoma by mucin and p53 immunohistochemistry. 1611 33

Most pancreatic neoplasia are of ductal lineage, characterized by tubule (gland), cyst, papilla, or mucin formation and expression of mucin-related glycoproteins and oncoproteins (eg, MUC1, CA19-9, CEA, DUPAN), as well as some subsets of cytokeratin (eg, CK19). Mutations of k-ras oncogene and DPC4 are also common in ductal neoplasia and generally not seen in nonductal tumors. A variety of pancreatic neoplasia fall under the heading of ductal neoplasia. Invasive ductal adenocarcinoma (DA) is the most important and constitutes the vast majority (>85%) of pancreatic tumors. DA is characterized by insidious infiltration and rapid dissemination, despite its relatively well-differentiated histologic appearance. In some variants of DA such as undifferentiated or sarcomatoid, evidence of ductal differentiation may be lacking or only focal. The presumed precursors of DA are microscopic intraductal proliferative changes that are now termed pancreatic intraepithelial neoplasia (PanIN). PanINs comprise a neoplastic transformation ranging from early mucinous change (PanIN-1A) to frank CIS (PanIN-3). A similar (in situ) neoplastic spectrum also characterizes intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, which are cystic ductal-mucinous tumors with varying degrees of papilla formation, and may be associated with invasive carcinoma. As such, these can be regarded as mass-forming preinvasive neoplasia. Some intraductal papillary mucinous neoplasms are associated with invasive carcinoma of the colloid type. Colloid carcinoma of the pancreas appears to be a clinicopathologically distinct tumor with indolent behavior. Whereas most ductal pancreatic neoplasia are characterized by some degree of mucin formation, serous tumors, of which serous (microcystic) adenoma is the sole example, lack mucin formation, presumably because they recapitulate centroacinar ducts. They are typically benign tumors. It is recognized now that pancreatic carcinoma, like other malignant processes, is a genetic disease produced by progressive mutations in cancer-related genes. These alterations can be categorized as "early" such as k-ras mutation, HER-2/neu, PSCA, MUC5, and fascin overexpression; "intermediate" such as p16 inactivation, MUC1, and cyclin D1 overexpression; and finally as "late" such as p53 and DPC4 inactivation, BRCA2 mutation, and overexpression of ki-67, 14-3-3sigma, and mesothelin. Ductal neoplasia is the most important category among pancreatic tumors. It is important to appreciate the different types of ductal tumors because they vary greatly in their clinicopathologic characteristics and prognosis. Understanding the molecular mechanisms of ductal carcinogenesis will help develop more efficient prevention and therapy of these tumors.
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PMID:Ductal neoplasia of the pancreas: nosologic, clinicopathologic, and biologic aspects. 1618 79

Because chromosomal chromosomal instability (CIN) and microsatellite instability (MSI) are important genetic alterations in colorectal cancers, we classified the sporadic colorectal cancers (CRC) on the status of the CIN and MSI and explored their molecular profiles. A total of 213 colorectal tumors were collected for analysis of DNA ploidy, MSI, loss of heterozygosity (LOH), mutation of p53 (exons 5 to 9), Ki-ras (exons 1 and 2) and BRAF (V599E). Relationships between clinicopathological variables and molecular analyses were analyzed with the chi(2) test (Yates' correction). Kaplan-Meier survival curves were compared using log-rank test. Variables with p < 0.1 were entered into the Cox regression hazard model for multivariate analysis. High microsatellite instability (MSI-H) existed in 19 tumors (8.9%), which were more likely to be right-sided (31.6%) with poor differentiation (26.3%). Seventy-one (33.3%) tumors were diploid and 142 (66.7%) were aneuploid. Mutations in p53, Ki-ras and BRAF were found in 45.1%, 41.8% and 4.2% of tumors, respectively. Based on MSI, and CIN, 3 classes were defined: (i) High microsatellite instability MSI-H tumors: young age, high carcinoembryonic antigen (CEA) level, right colon, poorly differentiated, mucin production, high BRAF mutation, lower allelic loss and relatively good prognosis; (ii) Microsatellite stability (MSS) diploid tumors: right colon, poorly differentiated, less infiltrative tumor, mucin production, lower allelic loss and low p53, BRAF mutation; (iii) MSS aneuploid tumors: more infiltrative invasion, greater allelic loss and high p53 mutation. According to multivariate analysis, tumor stage and p53 mutation were significantly associated with disease progression. The MSS diploid and MSS aneuploid CRCs could be subtyped with p53 mutation and had different prognostic outcome and molecular profiles. The 4-year disease-free survival (DFS) of patients with MSS-diploid, wild-type p53 tumors was 67% and significantly higher than those of patients with MSS-diploid, mutant p53 CRC (30%, p = 0.003). The same trend was found in patients with MSS-aneuploid CRC(wild p53 vs. mutant p53, 64% vs. 41%, p = 0.009). We concluded that CIN, MSI and p53 mutation status might be used as a multiple parameter profile for the prognosis of sporadic colorectal cancer.
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PMID:Relationship between genetic alterations and prognosis in sporadic colorectal cancer. 1623 16

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.
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PMID:Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix. 1626 Feb 76

The purpose of the present report was to examine the possibility of molecular pathological subtyping of mucinous adenocarcinomas (MAC) of the colorectum. Thirty-five formalin-fixed and paraffin-embedded MAC specimens of the colorectum were analyzed. Genetic alterations of p53 gene and microsatellite instability (MSI) as well as immunohistochemical analysis of mucin subtypes (human gastric mucin (HGM), anti-mucin monoclonal antibody recognizing gastric gland mucous cells-1, MUC2, CD10) and expression levels of human mutL homolog 1 (hMLH1), p53 and Ki-67 were performed. According to MSI and p53 status, these tumors were subclassified into three groups: mutator-type tumors with a high frequency of MSI (20%), suppressor/p53-type tumors with p53 mutation, p53 overexpression or loss of heterozygosity of D17S250 (an adjacent locus to p53; 40%) and the unclassified tumors (40%). The suppressor/p53-type tumors had a significant association with distal colon location (P = 0.019), venous invasion (P = 0.002), extent of lymph node metastasis (P = 0.007) and higher tumor stage (P = 0.018). In contrast, mutator-type tumors had frequent expression of HGM (P = 0.005) and prominent lymphocytic infiltration at the advancing front of the tumor (P = 0.005). These results indicate that MAC of the colorectum could be subclassified according to molecular pathological background, reflecting distinct clinicopathological and phenotypic characteristics.
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PMID:Molecular pathological subclassification of mucinous adenocarcinoma of the colorectum. 1628 91


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