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

Barrett's metaplasia is associated with an increased risk for adenocarcinoma. Adenocarcinoma develops through a multistep process characterized by defects in genes and morphological abnormalities. The early morphological changes of the process are called 'dysplasia'. Dysplasia is defined as an unequivocal neoplastic (premalignant) transformation confined within the basement membrane. For most Western pathologists malignancy is defined as invasion and characterized by a breach through the basement membrane. Japanese pathologists rely on cytological atypia and complex branching of crypts. Cytological and architectural abnormalities allow identification of dysplasia on routinely stained sections. A distinction is made between low- and high-grade dysplasia. The differential diagnosis between low-grade dysplasia and reactive changes can be difficult. Therefore a second opinion is strongly recommended, not only for high-grade dysplasia but also for low-grade. Immunohistochemistry for p53 and flow cytometry for detection of aneuploidy can support the diagnosis. Identification of dysplasia and malignancy depends on the number of biopsy samples examined. The minimum number of biopsies required has not yet been determined and depends partly on the length of the metaplastic segment. It has been proposed to sample with four quadrant biopsies at 20-mm intervals. New endoscopic techniques can increase the diagnostic yield. Endoscopically visible lesions increase the risk of finding malignancy. The time sequence for the progression of dysplasia is not known but progression from low- to high-grade and cancer has been shown to occur over a period of years although it may not be inevitable.
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PMID:The diagnosis of dysplasia and malignancy in Barrett's oesophagus. 1093 Dec 31

Adenocarcinoma of the esophagus (ADCE) with Barrett's mucosa and adenocarcinoma of the cardia (ADCC) are often reported as a single pathological entity. In this study we have used strict anatomical-pathological criteria to distinguish between these two lesions and we have investigated their differences in TP53 mutations, MDM2 gene amplification, and cytokeratin expression. DNA was extracted from the tumor areas of formalin-fixed, paraffin-embedded sections in 26 ADCC and 28 ADCE patients. TP53 mutations were detected by temporal temperature gradient electrophoresis and identified by sequencing. MDM2 amplification was assessed by differential polymerase chain reaction. The expression of cytokeratins 4, 7, and 13 was examined by immunohistochemistry. In ADCC, the male to female ratio was 1.8:1, compared to 27:1 in ADCE. Five ADCC patients had a history of other neoplasms, compared to only one ADCE patient. The two types of tumor differed in the prevalence of TP53 mutations (31% in ADCC and 50% in ADCE) and of MDM2 gene amplification (19% in ADCC and 4% in ADCE), and in the pattern of expression of cytokeratin 7 (positive in 100% of ADCE and in 41% of ADCC) and cytokeratin 13 (positive in 81% of ADCE and in 36.5% of ADCC). ADCE and ADCC differ in their clinical characteristics, in the prevalence of TP53 mutations and MDM2 amplifications, and in the patterns of cytokeratin expression. These results support the notion that ADCC and ADCE are distinct pathological entities.
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PMID:Molecular and clinical differences between adenocarcinomas of the esophagus and of the gastric cardia. 1114 76

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.
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PMID:Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. 1143 14

Adenocarcinoma of Bartholin gland is a very rare disease and its molecular pathological features are poorly delineated. A 92-year-old woman with mucinous adenocarcinoma of Bartholin gland with metastasis to the right inguinal lymph node was treated with radiation therapy alone. Despite intensive radiation therapy, the tumor was locally recurrent and the patient died 10 months after radiation therapy. We searched for the presence of human papillomavirus 16 and 18 DNA and the expression of p53 protein, CA19-9, CEA and MIB-1 antigen. Immunohistochemical study showed that mucinous adenocarcinoma of Bartholin gland produced CA19-9 and CEA.
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PMID:Mucinous adenocarcinoma of Bartholin gland treated with radiation therapy: a case report. 1145 Sep 99

Retrorectal cyst hamartoma (RCH) is a rare benign cystic lesion located in the retrorectal space. Malignancy arising in such lesions is very uncommon. In this study, 2 cases of mucinous adenocarcinoma arising in RCH are presented. In one case, dysplastic epithelium lined the cyst wall, surrounding the area of carcinoma and suggesting a dysplasia-carcinoma progression in RCH. Adenocarcinoma and the dysplastic epithelium were strongly positive for p53 and Ki-67 and showed negative staining for p21 by immunohistochemistry. These findings are suggestive of a mutation in the p53 gene in the adenocarcinoma and in dysplastic epithelium lining the cysts, similar to the dysplasia-carcinoma sequence described for the development of colonic adenocarcinoma.
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PMID:p53 Mutation in adenocarcinoma arising in retrorectal cyst hamartoma (tailgut cyst): report of 2 cases--an immunohistochemistry/immunoperoxidase study. 1157 Sep 17

Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa is a rare tumor, with only 15 cases reported to date. We report a case in a 61-year-old man complaining of dysphagia. The upper endoscopy revealed that the tumor measured 3 cm and was 22 cm distant from the incisivors. A hiatal hernia with erosive esophagitis of the distal esophagus was present. On microscopic examination the tumor corresponded to a poorly differentiated adenocarcinoma immunoreactive for cytokeratin (CK) 7 and p53. The surrounding heterotopic gastric mucosa contained foci of intestinal metaplasia immunoreactive for CK7 in the surface epithelium and the entire glands and CK20 in the superficial epithelium and superficial glands. The CK7 and p53 positivity that we observed is very common in Barrett's adenocarcinomas. Moreover, intestinal metaplasia in heterotopic gastric mucosa shows the same CK7/CK20 pattern as specialized Barrett's mucosa. These common features shared by adenocarcinomas of the upper esophagus arising in heterotopic gastric mucosa and adenocarcinoma of the lower esophagus developing on Barrett's mucosa suggest that those two types of cancer have a common pathogenesis, related to gastroesophageal reflux disease.
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PMID:Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa: common pathogenesis with Barrett's adenocarcinoma? 1251 6

Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (> 20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.
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PMID:Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine. 1294 Apr 38

Adenocarcinoma of the pancreas is refractory to chemotherapeutic agents, including BCNU and streptozotocin. We have previously shown that drugs, which adduct the O(6)- position of guanine, are ineffective against pancreatic tumor cell lines because of high expression of O(6)-methylguanine-DNA methyltransferase (MGMT). The effect of MGMT inactivation on the resistance of pancreatic tumors to carmustine (BCNU) and to temozolomide (TMZ) was examined in five human pancreatic tumor xenografts in athymic mice. Tumor-bearing mice were treated: (a) with a single i.p. injection of BCNU or TMZ at the maximum-tolerated doses of 75 and 340 mg/m(2), respectively; and (b) with O(6)-benzylguanine (BG) or O(6)-benzyl-2'-deoxyguanosine (dBG) in combination with BCNU or TMZ. Pretreatment with the MGMT inactivators BG or dBG reduced the maximum-tolerated doses of BCNU and TMZ to 35 and 170 mg/m(2), respectively. MIA PaCa-2, CFPAC-1, PANC-1, CAPAN-2, and BxPC-3 having MGMT levels of 890, 1680, 680, 900, and 330 fmol/mg protein, respectively, were unresponsive to BCNU. MIA PaCa-2 and CFPAC-1 were also unresponsive to TMZ, whereas CAPAN-2 responded with a tumor delay of 32 days. BG or dBG sensitized all tumors to both BCNU and TMZ. BG plus BCNU treatment of MIA PaCa-2, CFPAC-1, PANC-1, CAPAN-2, and BxPC-3 induced tumor delays of 18, 16, 12, 14, and 16 days, respectively. In comparison, dBG plus BCNU at doses that were equitoxic to BCNU plus BG yielded tumor delays of 30, 19, 16, 21, and 22 days, respectively. The pancreatic tumors tested displayed functional mismatch repair that, however, may not be always sufficiently restrictive to prevent mutations under alkylation stress. Treatments with either BCNU or TMZ resulted in some degree of mutation in recurring tumors with the exception of CAPAN-2, the only wt-p53 xenograft. dBG, a weak MGMT inactivator in vitro as compared with BG, was markedly more effective than the latter in enhancing the efficacy of BCNU against pancreatic tumor xenografts. Both BG and dBG also enhanced the efficacy of TMZ against pancreatic tumors, possibly because of the repression of MGMT, which cannot be achieved with TMZ treatments alone. These results suggest that pancreatic tumors, which are resistant to DNA alkylating agents, may be sensitized to such agents when pretreated with MGMT inactivators.
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PMID:Sensitization of pancreatic tumor xenografts to carmustine and temozolomide by inactivation of their O6-Methylguanine-DNA methyltransferase with O6-benzylguanine or O6-benzyl-2'-deoxyguanosine. 1450 74

Adenocarcinoma of the small intestine (ACSI) is a rare condition with few studies addressing follow-up and prognosis. Tumors of 35 patients with curative resection of an ACSI were retrospectively analyzed by immunohistochemistry: p53, hMLH1, hMSH2 and hMSH6 and microsatellite instability (MSI): BAT-26, BAX, TGF-beta RII. With a median follow up of 6.1 years, the median cancer-specific survival (CSS) was 36.2 months. Patients who were highly instable (MSI-H) (n=10) had a CSS of 49.6 months in contrast to patients with stable tumors (23.2 months) (P=0.010). Additionally, a low tumor stage according to UICC and MSI-H were shown to be independent factors (P=0.005 and P<0.001) for an increased survival in multivariate analysis. Therefore, it is suggested that analysis of the MSI status might prove useful in discerning prognosis within cancers of the same stage.
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PMID:Prognostic significance of microsatellite instability in curatively resected adenocarcinoma of the small intestine. 1473 26

Barrett's esophagus is the result of chronic injury which is usually caused by gastroesophageal reflux. NF-kappaB is expressed in the reflux esophagitis. Specialized columnar epithelium (SCE) is characteristic of Barrett's esophagus and has a malignant predisposition. SCE expresses Cdx1 and Cdx2. Adenocarcinoma in Barrett's esophagus is believed to develop through the metaplasia-dysplasia-carcinoma sequence. P53, beta-catenin, PPARgamma, and estrogen receptor beta are closely related to the development of esophageal carcinogenesis.
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PMID:[Expression of transcription factor in Barrett's esophagus]. 1610 Dec 23


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