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Microsatellite instability and alteration of E2F‐4 gene in adenosquamous and squamous cell carcinomas of the stomach
Author(s) -
Woo Dong Kyun,
Lee Won Ae,
Kim Yong Il,
Kim Woo Ho
Publication year - 2000
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1046/j.1440-1827.2000.01105.x
Subject(s) - microsatellite instability , carcinogenesis , biology , cancer research , cancer , adenosquamous carcinoma , dna mismatch repair , pathology , adenocarcinoma , stomach cancer , gene , medicine , genetics , microsatellite , colorectal cancer , allele
Microsatellite instability (MSI) due to defective DNA mismatch repair (MMR) is a form of genomic instability underlying the tumorigenesis of various human neoplasms. To evaluate the roles of MSI in the pathogenesis of gastric carcinomas with squamous differentiation, 17 primary stomach cancer patients (15 adenosquamous and two squamous cell carcinomas) were examined for MSI frequency using five microsatellite markers and the criteria for MSI recommended by the National Cancer Institute Workshop. The molecular causes and consequences of MSI in these neoplasms were further researched through the immunohistochemistry of MMR proteins and the mutational analysis of cancer‐associated genes targeted by MSI, respectively. Two of the 17 (12%) cases demonstrated MSI at the most examined loci and were classified as having high level MSI (MSI‐H). These tumors also exhibited frame‐shift mutations at mononucleotide repeats in the target genes, including TGF β RII , IGFIIR , BAX , and hMSH6 . It is interesting to note that the mutations of the serine (AGC) 13 repeats within the E2F‐4 gene were found only in the squamous cell carcinoma portions of them, whereas such alterations were not detected in any of the adenocarcinomatous portions. This suggests that E2F‐4 might be implicated in the transformation of adenocarcinoma into squamous cell carcinoma and further studies are needed to understand its role in squamous differentiation.