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Multidrug Resistance in Hepatocellular Carcinoma

In addition, there are large deletions in EPCAM , which can lead to transcriptional silencing of MSH2 .3 Pathogenic MMR germline mutation confers a high risk of development of a somatic second-hit mutation, with subsequent genomic instability and development of cancer in affected people.3 Lynch syndrome has historically been characterized by an increased lifetime risk 10%75% of colorectal cancer.3 , 4 The lifetime risk of endometrial cancer in females with Lynch syndrome has been reported to exceed that of colorectal cancer, ranging from 8.4% to 71%.3 , 4 Affected people have a risk of ovarian cancer of 6%14%, compared to 2%3% in the general population.1 , 4 Affected people also have an increased risk of gastric (0.7%13%), small bowel (0.6%12%), pancreatic (0.4%6%) and urothelial (1.9%15%) cancers.3 , 4 Screening strategies for Lynch syndrome in people with endometrial cancer include clinical historybased criteria (e.g., Amsterdam and Bethesda criteria5 8), tumour microsatellite instability (MSI) testing and tumour immunohistochemical (IHC) testing