Background/aims: In order to identify microsatellite instability (MSI), the test based on the polymerase chain reaction (PCR) can be used. However, PCR is not routinely performed in all hospital laboratories. Recently, immunohistochemistry (IHC) for MLH1 and MSH2 proteins has been reported as a rapid and useful method for MSI. However, the efficacy of IHC in the detection of the MSI has not been well established. The aim of this study was to evaluate the usefulness of IHC in the detection of the MSI by comparing it with the test results using PCR in colorectal cancer (CRC).
Methods: Paraffin-embedded normal and tumor tissues from seventy-five patients who underwent surgical resection of CRC were used. Abnormal expression of MLH1 and MSH2 protein was determined by IHC using MLH1 and MSH2 antibodies. Normal and tumor DNAs were obtained from thirty CRC tissues that showed abnormal expression of MLH1 and MSH2 proteins by IHC. The MSI status was confirmed by PCR using five markers.
Results: Thirty tumors showed abnormal expression of MLH1 and MSH2 proteins by IHC, but only three tumors out of them were confirmed to have MSI by PCR.
Conclusions: This result suggests that IHC with MLH1 and MSH2 antibodies does not seem to be a useful method to identify MSI in CRC, therefore PCR is required for detection of the MSI.
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Clin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFJ Pers Med
December 2024
Global Medical and Scientific Affairs, MSD, Mexico City 01090, Mexico.
: Mismatch repair (MMR) status is an important prognostic and predictive indicator in cancer, distinguishing proficient (pMMR) tumors from deficient (dMMR) ones. This study aimed to determine the prevalence of dMMR in colorectal (CRC) and selected non-CRC solid tumors (gastric, esophageal, and endometrial cancers). : This retrospective study was conducted at a private health institution in Mexico City, analyzing patients diagnosed with colorectal, gastric, esophageal, or endometrial cancer from January 2017 to December 2020.
View Article and Find Full Text PDFCurr Issues Mol Biol
December 2024
Department of Pathology, Analiza, 28001 Madrid, Spain.
Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC).
View Article and Find Full Text PDFClin Genet
December 2024
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Broad-spectrum genetic tests often lead to the identification of variants of uncertain significance (VUS), a major issue in modern clinical genetics. A fair proportion of VUS may alter the splicing processes, but their interpretation is challenging. This study aimed at providing a classification approach for VUS potentially-affecting splicing by integrating transcript analysis from peripheral blood mRNA into routine diagnostics.
View Article and Find Full Text PDFFam Cancer
December 2024
Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous variants in the DNA mismatch repair genes- MLH1, MSH2, MSH6 and PMS2, with the majority detected in MLH1 and MSH2. Recurrently observed LS-associated variants in apparently unrelated individuals have either arisen de novo in different families due to mutation hotspots or are inherited from a common ancestor (founder) that lived several generations back.
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