We retrospectively analyzed the expression of E-cadherin, CD44, and MSH2 in 223 paraffin-embedded stage II and III CRC specimens using immunohistochemistry in the training cohort.
Notably, in both MSI-H and MSS CRC, CD274<sup>IC</sup> and CD274<sup>IP</sup> were independently associated with improved prognosis (P < 0.05), while BRAF mutation was associated with CD274<sup>TP</sup>, poor differentiation, sporadic type, and hMLH1(-)/hMSH2(+)/hMSH6(+)/PMS2(-) in MSI-H CRC (P < 0.006).
We studied the immunohistochemical expression of MSH2, MSH6, and Ki-67 in MSS colorectal carcinoma with (n=50) or without (n=64) preoperative neoadjuvant therapy and Lynch syndrome-associated colorectal carcinoma with confirmed MSH6 germline mutation (n=3).
It is of note that mucinous tumour is one of the frequent histological features of colorectal cancer (CRC) in Lynch syndrome (LS), an autosomal dominantly inherited disease caused by a germline mutation of the DNA mismatch repair (MMR) genes including human mutL homolog 1 (MLH1), human mutS homolog 2 (MSH2), human mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2).
We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC.
Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O.
Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC and LS associated cancers.
A significantly higher frequency of target gene mutations was observed in CRC from patients with germline mutations in MLH1 or MSH2 when compared with MSH6.
Immunohistochemistry for β-catenin, CD133, CD44 and the mismatch-repair markers hMLH1 and hMSH2 was applied to primary specimen of two CRC cohorts with CNS (n=29) and exclusive liver metastasis (n=36).
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6.
Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancers as well as a 9-12% lifetime risk of ovarian cancer.
Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-deficient colorectal cancer (non-Lynch syndrome families).
On average, one in 71 male and one in 102 female MLH1 or MSH2 mutation carriers in their 20s will be diagnosed with colorectal cancer in the next 5 years.
Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM.
Telomere shortening and its potential correlation with clinicopathological predictive markers in sporadic colorectal cancer (CRC) with normal expression of mismatch repair (MMR) proteins (including Mlh1, Msh2, Pms2, and Msh6) and normal p53 expression was completely explored.
Therefore, we carried out this study with 433 primary sporadic CRC patients to investigate the associations between germline and somatic hMLH1/hMSH2 gene mutations, hMLH1 promoter methylation, and the overall survival (OS) of CRC; to evaluate the effect of interaction between gene mutation and methylation on the risk of CRC prognosis.