The rate of patients with lesions containing both mutL homolog 1 (MLH1) methylation and microsatellite stable status was 66.7% in those with synchronous CRC, with at least one lesion with high microsatellite instability.
Approximately 15% to 20% of colorectal cancers are developed through the serrated pathway of tumorigenesis, which is associated with BRAF mutation, CpG island methylation phenotype, and MLH1 methylation.
Compared with the surrounding normal mucosa, SPTAN1 expression was reduced in MLH1-deficient CRCs, whereas MLH1-proficient CRCs showed a significant upregulation of SPTAN1.
To describe the frequencies of mismatch repair deficiency (dMMR), BRAFV600E mutations and MLH1 methylation in resected CRC, and evaluate the impact of universal screening on LS detection.
The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development.
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.
Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear.
In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer.
Although the presence of HER2 amplifications and oncogenic mutations in KRAS, NRAS, and BRAF are associated with EGFR-targeted therapy resistance, for a large population of CRC patients the underlying mechanism of RAS-MEK-ERK hyperactivation is not clear.
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).
Notably, true tumor cell PD-L1 expression in colorectal carcinoma was rare, present in only 3 of 129 tumors (2.3%): 2 MLH1-methylated and 1 mismatch-repair-proficient with high tumor-infiltrating-lymphocytes; and the staining in the tumor cells in all 3 was diffuse (>=50% of the tumor).
In the multivariate setting, left-sided CRC only turned out as a significant positive prognostic parameter regarding progression-free survival, irrespective of the type of chemotherapy or BRAF and NRAS mutations.
In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status.
We compared the development of (advanced) adenomas and CRC among patients with pathogenic variants in the DNA mismatch repair genes MLH1 (n=55), MSH2 (n=44), MSH6 (n=143), or PMS2 (n=22) over 1836 years of follow-up (median follow-up of 6 years per patient).
To further investigate the role of Wntless in tumorigenesis, APC-deficient spontaneous intestinal tumors and chemical induced colorectal cancer mouse models were employed.
The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation.