The APC promoter is hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and adenoma (n = 48), and neoplasia with APC methylation fails to express the APC transcript.
The risk of colorectal cancer in carriers of such EPCAM deletions is comparable to that of MSH2 mutation carriers, and is in accordance with a high expression of EPCAM in colorectal cancer stem cells.
In cases and controls, average MLH1 expression in the ascending colon tended to be lower with increased age [by 56% (P = 0.02) and 25% (P = 0.16), respectively, for those > or =55 years], and with a history of colorectal cancer in a first-degree relative (by 22% [P = 0.56] and 34% [P = 0.16], respectively).
These results suggest that the inactivation of the APC gene is very common in sporadic colorectal cancer, and the main inactivation mechanism of the APC gene is promoter hypermethylation.
Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers.
In this retrospective study for quality assessment of a next-generation sequencing assay, we examined BRAF, KRAS, and NRAS genes within the mitogen-activated protein kinase (MAPK) pathway and the PIK3CA gene within the phosphatidylinositol 3-kinase (mTOR) pathway in 744 CRC specimens submitted to our clinical diagnostics laboratory.
The higher gene expression of MSH2 in responders and the trend for predicting overall survival indicates a predictive value of this marker in the treatment of advanced CRC with capecitabine.
The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ.
Paraffin embedded tissue samples of colorectal cancers from 46 patients were assessed for mismatch repair protein expression (hMLH1 and hMSH2) by immunohistochemistry.
High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2.
The proximal MSI-H CRC was predominantly in female (p=0.014), had a more aggressive differentiation (p=0.001), was of advanced stage (p=0.035), and had a frequent loss of MLH1 expression (p=0.005) compared to the distal MSI-H CRC.
Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas.
: By using gene array profiling, NF-kappaB target gene expression was assessed in CRCs that expressed human mutL homolog 1 (hMLH1), hMSH2, and nuclear beta-catenin by comparing expression at the IF, in the TC, and in normal mucosa.