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

We present a case of mucoepidermoid carcinoma of the anal canal, with special reference to immunohistochemical analysis of the tumor to clarify its histogenesis. A 36-year-old man underwent surgery for mucoepidermoid carcinoma of the anal canal. Immunohistochemical analysis of the resected specimen was performed. Serial sections were stained immunohistochemically by the labeled streptavidin-biotin peroxidase method for various antigens, including epithelial membrane antigen (EMA); carcinoembryonic antigen (CEA); different types of cytokeratins, including CK10 and CAM 5.2; and p53 oncoprotein. The solid component of the tumor cells was immunohistochemically positive for EMA, CEA, and CAM 5.2, but negative for CK10. These staining patterns were different from those of anal squamous epithelium. These results confirm that mucoepidermoid carcinoma of the anus may arise from the anal transitional zone, and that it is biologically different from squamous cell carcinoma of the anus.
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PMID:Mucoepidermoid carcinoma of the anal canal: an immunohistochemical study. 1148 Jul 98

The molecular mechanisms involved in progression of squamous cell carcinoma of the anus (SCCA) are poorly elucidated, as well as the potential role of HIV infection. Loss of heterozygosity (LOH) is one of the mechanisms responsible for inactivation of tumor suppressor genes. We hypothesized that HIV-induced immunosuppression may contribute to an alternate molecular pathway in SCCA progression, through persistence of human papillomavirus infection within the anal canal. This study was undertaken to compare the molecular biology of SCCA in HIV-positive (HIV+) and HIV-negative (HIV-) patients. We retrieved tumor specimens from 18 HIV- and 10 HIV+ patients diagnosed with SCCA in two institutions. DNA from tumor and normal tissues was extracted and then amplified by polymerase chain reaction. LOH was investigated at 14 loci: three at 18q (DCC), two at 13q (Rb), three at 17p (p53), three at 11q, one at 2p, and two at 5q (APC). LOH was defined by a tumor DNA-to-normal tissue DNA ratio of >2. HIV+ patients were younger (36 +/- 7 years versus 53 +/- 13 years, P=0.001) and showed a trend toward tumors of larger size (3.7 +/- 1.6 cm versus 2.6 +/- 1.5 cm, P=0.09). The median CD4+ count in HIV+ patients at the time of diagnosis was 74 x 10(6)/L (range, 5-900). The overall frequency of LOH was 17.3% (41 LOH of 236 informative loci). Tumors in HIV- patients were more likely to present LOH than were tumors in HIV+ patients (24.1% versus 6.6%, P=0.0004). Differences between the two groups with regard to allelic losses were also observed at specific loci, such as 18q (41% [HIV-] versus 0% [HIV+], P=0.05), 17p (43% versus 10%, P=0.09), and 5q (33% versus 0%, P=0.12). Consistent LOH on chromosomes 17p, 18q, 5q, and 11q were observed in HIV- patients with SCCA. By contrast, allelic losses at 17p, 5q, and 18q seem to be rare in tumors of HIV+ individuals. These data suggest that immunosuppression may promote SCCA progression through an alternate pathway and that persistence of HPV infection within the anal canal may play a central role in this process.
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PMID:Molecular biology of squamous cell carcinoma of the anus: a comparison of HIV-positive and HIV-negative patients. 1558 90

Anal squamous cell carcinoma (ASCC), either with human papillomavirus (+) or (-), is a neoplastic disease with frequent recurrence and metastasis. To characterize ASCC genomes, we attempted to disclose novel alterations of ASCC genomes and other genetic features including mutation signatures. We performed whole-exome sequencing and copy number alteration (CNA) profiling for 8 ASCC samples from 6 patients (2 cases with primary and recurrent/metastatic tumors). We found known ASCC mutations (TP53, CDKN2A, and PIK3CA) and CNAs (gains on 3q and 19q and losses on 11q and 13q). In addition, we discovered novel mutations in HRAS and ARID1A and CNAs (gain on 8q and losses 5q, 9p, 10q, and 19p) that had not been reported in ASCCs. We identified 4 signature patterns of the mutations (signatures 1 and 2 with deamination of 5-methyl-cytosin, signature 3 with APOBEC, and signature 4 with mismatch repair) in the ASCCs. Although signatures 1 to 3 have been detected in other SCCs, signature 4 was first identified in ASCCs. In addition, we first found that ASCCs harbored chromothripsis, copy-neutral losses of heterozygosity, and focal amplification of KLF5 super-enhancer. Analyses of primary and recurrent/metastatic pair genomes revealed that driver events in development and progression of ASCC might not be uniform. Our data indicate that ASCCs may have similar mutation and CNA profiles to other SCCs, but that there are unique genomic features of ASCCs as well. Our data may provide useful information for ASCC pathogenesis and for developing clinical strategies for ASCC.
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PMID:Whole-exome sequencing identified mutational profiles of squamous cell carcinomas of anus. 2955 73