Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bcl-2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bcl-2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy.
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PMID:Primary undifferentiated small cell carcinoma of the esophagus. 1002 52

Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser-captured microdissection of human SCCIS and adjacent epidermis to isolate genomic DNA and RNA for next generation sequencing. Whole exome sequencing (WES) identified UV-signature mutations in multiple genes including Notch 1-3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS. Gene families, including SCHLAFEN genes, contained UV/oxidative-signature disruptive (UVD) epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1166 differentially expressed genes; the top 5 enriched GO biological processes included: 1) immune response, 2) epidermal development, 3) protein phosphorylation, 4) regulation of catalytic activity, 5) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. Neuralized 1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.
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PMID:Whole exome and transcriptome analysis of UV-exposed epidermis and carcinoma in situ reveals early drivers of carcinogenesis. 3264 44