UNIPROT:P04637 - FACTA Search

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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group.
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PMID:Is mucinous carcinoma of the colorectum a distinct genetic entity? 851 44

Seven (3.3%) of 213 patients who underwent surgery for early colorectal cancer (invasion limited to no deeper than the submucosa) at the National Cancer Center Hospital, Tokyo, between 1986 and 1995 had synchronous (2 patients) or metachronous (5 patients) liver metastases. The average period from surgical resection of the primary colorectal cancer to the diagnosis of liver metastases was 25 months (range, 0-52 months). The clinicopathologic and immunohistochemical features of the primary lesions in these patients were compared with these features in the lesions in consecutive patients with early colorectal cancer who had no evidence of liver metastases within at least 5 years after colorectal resection. Venous invasion was more frequent in the primary lesions with liver metastases than in those without liver metastases (57% vs 0%; P = 0.0035). Expression of p53 and CD44v9 was more frequent in the primary lesions with liver metastases (71% and 100%) than in those without metastases (56% and 72%). In contrast, MUC2 expression was more frequent in the primary lesions without liver metastases (72%) than in those with metastases (43%). Venous invasion is considered to be closely related to liver metastasis, and the immunohistochemical expression of p53 and CD44v9 provides useful information for identifying those patients with early colorectal cancer who have a high risk of developing liver metastases.
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PMID:Clinicopathologic and immunohistochemical study of early colorectal cancer with liver metastases. 1043 8

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.
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PMID:Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities. 1072 20

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.
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PMID:Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant. 1075 96

There is a need for new prognostic parameters that could add insights into the aggressiveness of tumors. Because the expression of two well-characterized mucin antigens, MUC1 and MUC2, in colorectal adenocarcinomas (CRCs) has been correlated with the aggressiveness of CRCs, we evaluated the prognostic value of the expression of MUC1 and MUC2 in CRCs collected from African-American and Caucasian patients. Expression of MUC1 and MUC2 was evaluated by immunohistochemistry in 166 archival CRC specimens collected from 58 African-American and 108 Caucasian patients that had been analyzed previously for nuclear accumulation of p53 (p53nac). Univariate Kaplan-Meier and multivariate Cox proportional hazards models were used to determine the prognostic significance of expression of MUC1 and MUC2 in these CRCs. MUC1 expression was more frequent in advanced stage CRCs, whereas MUC2 expression was higher in the mucinous type of CRCs. Although similar proportions of CRCs from African-Americans and Caucasians expressed MUC1 and MUC2, the MUC1 expression was found to be an indicator of high risk of death from CRC in Caucasians (hazard ratio, 2.03; P = 0.038) but not in African-Americans. Furthermore, Caucasians with CRCs exhibiting concomitant expression of MUC1 and p53nac demonstrated the lowest probability of overall survival (log rank test, P = 0.004). No prognostic value was found for MUC2 alone or in combination with p53nac in either group of patients. Expression of MUC1 in CRCs is a valuable indicator of poor prognosis in Caucasian patients. Additionally, combined evaluation of MUC1 and p53nac increases the ability to identify Caucasian patients with aggressive subtypes of CRC and may be useful in selecting or in developing novel therapeutic regimes.
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PMID:Racial differences in the prognostic usefulness of MUC1 and MUC2 in colorectal adenocarcinomas. 1105 Dec 51

The incidence of colorectal carcinoma is increasing in Japan. Malignant transformation in colorectal neoplasia is usually considered to be owing to adenoma-carcinoma sequence. Elucidation of the recent alteration in the biological properties of colorectal adenoma is sure to be useful to understand the recent increase of the colorectal carcinoma in Japan. We compared the histopathological feature, mitotic index, proliferative activity (Ki-67 labeling index), expression of glycoproteins such as MUC2 mucin, sialyl Lewis A (SLe(a)) and sialyl dimeric Lewis X (SLe(x)), and p53 protein overexpression, between 108 adenomas in the old period (Group A, from 1969 to 1985) and 140 adenomas in the recent period (Group B, from 1995 to 1998). The histological dysplasia, mitotic index and Ki-67 labeling index of the adenomas were significantly higher in Group B than in Group A. In contrast, the expression of MUC2 mucin, which is considered to be a differentiation factor of intestinal mucosal epithelium, was significantly reduced in Group B than in Group A. The SLe(a) and SLe(x) expressions showed no significant difference between them. The p53 expression showed no significant difference between them, except for the moderate dysplasia. These findings indicate that recent colorectal adenomas show more advanced degrees of histological dysplasia, more rapid growth, and reduced differentiation than colorectal adenomas, which developed at earlier times, and may be related with the recent high incidence of colorectal carcinoma in Japan.
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PMID:Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan. 1144 34

The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.
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PMID:Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas. 1185 May 85

Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile. To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas. The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.
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PMID:The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. 1191 24

Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <.05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <.001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-beta type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =.046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.
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PMID:Distinct clinical features and outcomes of gastric cancers with microsatellite instability. 1206 77

Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression.
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PMID:Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver. 1209 75

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