Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer.
Mismatch repair (MMR) protein expression was analyzed through histopathological/immunohistochemistry assays, which was sparse in 5 CRC patient's colorectal tissues (12%).
We investigated the consistence of MMR status as well as MSI between primary CRC and metastatic tumor to see if the expression of four MMR proteins and the status of MSI are congruent in primary tumor and metastatic tumor.
Many colorectal cancers (CRCs) that exhibit microsatellite instability (MSI) are not explained by MLH1 promoter methylation or germline mutations in mismatch repair (MMR) genes, which cause Lynch syndrome (LS).
Patients with colorectal cancer (CRC) with mismatch repair-deficient (dMMR) tumours without <i>MLH1</i> methylation or germline MMR pathogenic variants (PV) were previously thought to have Lynch syndrome (LS).
However, defects in Human Leukocyte Antigen (HLA) class I expression were reported to occur in most MMR-d CRCs, which would preclude antigen presentation in these tumours, considered essential for the clinical activity of this immunotherapeutic modality.
Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin.
A comprehensive molecular characterization of colorectal cancer (CRC) tissues was carried out by immunohistochemistry of MMR proteins, Microsatellite Instability (MSI) assay, methylation specific MLPA and transcript analyses.
IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features.
Detailed morphological evaluation, immunohistochemical analysis of mismatch repair (MMR) proteins, p53 and O<sup>6</sup>-methylguanine DNA methyltransferase (MGMT) expression and molecular analysis for KRAS, NRAS and BRAF gene mutation were performed in the retrieved CRC cases as well as in the detected dysplasia and PPLs of these patients.
In the present review, we also report the recent discoveries in molecular genetics of LS, such as the new roles of MMR protein and immune response of MMR repair deficiency in colorectal cancer.
Clinical outcomes of checkpoint blockade immunotherapy on colorectal cancer (CRC) are influenced by mismatch repair (MMR) gene status, which is associated with distinct tumor immune infiltrates and systemic inflammatory response status.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes.
The aim of the present study was to stratify CRC patients using molecular diagnostics and next generation sequencing, according to the chosen criteria [positive for microsatellite instability (MSI) and negative for a <i>BRAF</i> mutation and <i>MutL homolog 1</i> (<i>MLH1</i>) methylation], and subsequently to detect pathological germline mutations in MMR genes in Slovak patients.
Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins.
Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC).
In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in colorectal carcinoma with MMR protein deficiency and BRAF mutation.
MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma.
TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer.
Mismatch repair deficient (dMMR) colorectal cancer (CRC) is caused by inactivation of the MMR DNA repair system, most commonly via epigenetic inactivation of the MLH1 gene, and these tumors occur most frequently in the right colon.