Abstract
BackgroundMicrosatellite instability (MSI) at tri- or tetranucleotide repeat markers (elevated microsatellite alterations at selected tetranucleotide repeat, EMAST) has been recently described. But, the underlying genetic mechanism of EMAST is unclear. This study was to investigate the prevalence of EMAST, in type I endometrial carcinoma, and to determine the correlation between the MSI status and mismatch repair genes (MMR) or p53.MethodsWe examined the 3 mono-, 3 di-, and 6 tetranucleotide repeat markers by PCR in 39 cases of type I endometrial carcinoma and performed the immunohistochemistry of hMSH2, hMLH1, and p53 protein.ResultsMore than two MSI at mono- and dinucleotide repeat markers was noted in 8 cases (MSI-H, 20.5%). MSI, at a tetranucleotide repeat, was detected in 15 cases (EMAST, 38.5%). In remaining 16 cases, any MSI was not observed. (MSS, 42.1%), MSI status was not associated with FIGO stage, grade or depth of invasion. The absence of expression of either one of both hMSH2 or hMLH1 was noted in seven (87.5%) of eight MSI-H tumors, one (6.3%) of 16 MSS tumors, and five (33.3%) of 15 EMAST tumors. (p = 0.010) The expression of p53 protein was found in one (12.5%) of eight MSI-H tumors, five (31.3%) of 16 MSS tumors, and seven of 15 EMAST tumors. (p = 0.247)ConclusionOur results showed that about 38.5% of type I endometrial carcinomas exhibited EMAST, and that EMAST was rarely associated with alteration of hMSH2 or hMLH1.
Highlights
Microsatellite instability (MSI) at tri- or tetranucleotide repeat markers has been recently described
The genetic basis for MSI associated with defective mismatch repair genes (MMR) is being increasingly clarified, the mechanism underlying microsatellite alterations for elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) tumors remains to be unclear [3]
It has been shown to be present in 25% to 30% of type I endometrial carcinoma, which is related with estrogenic stimulation, and has been rarely demonstrated in type II endometrial carcinoma, which is unrelated with estrogen [10,11,12]
Summary
Microsatellite instability (MSI) at tri- or tetranucleotide repeat markers (elevated microsatellite alterations at selected tetranucleotide repeat, EMAST) has been recently described. This study was to investigate the prevalence of EMAST, in type I endometrial carcinoma, and to determine the correlation between the MSI status and mismatch repair genes (MMR) or p53. Inherited defects in DNA mismatch repair (MMR) genes, usually hMLH1 or hMSH2, lead to microsatellite instability (MSI) and subsequent malignancy in hereditary nonpolyposis colon cancer (HNPCC) [1]. The genetic basis for MSI associated with defective MMR is being increasingly clarified, the mechanism underlying microsatellite alterations for EMAST tumors remains to be unclear [3]. The aim of the current study was to evaluate the prevalence and clinicopathologic significance of MSI including EMAST in sporadic type I endometrial carcinoma. We examined the association between hMLH1, hMSH2 or p53 and EMAST using immunohistochemical staining techniques
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