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Universal Screening Considered Beneficial for Upper Tract Urothelial Carcinoma Along Endometrial & Colorectal Cancer Patients

Heredity non-polyposis colorectal cancer syndrome is also called as Lynch syndrome. Colorectal and Endometrial cancers are generally microsatellite instability-high cancers. Mutations occur when DNA in cancer cells repair its self with problematic replication. Mutations in DNA then create replication with errors which causes microsatellite instability. Lynch syndrome is a genetic disease which increases the chances [...]

Heredity non-polyposis colorectal cancer syndrome is also called as Lynch syndrome. Colorectal and Endometrial cancers are generally microsatellite instability-high cancers. Mutations occur when DNA in cancer cells repair its self with problematic replication. Mutations in DNA then create replication with errors which causes microsatellite instability.

Lynch syndrome is a genetic disease which increases the chances of endometrial or colon cancer in those who have it so universal screening is an important measure of safety. Along with this upper tract urothelial carcinoma is also observed in 4-6% of Lynch Syndrome’s patients.

Immunohistochemistry is used to find the mismatch repair loss pattern in Lynch Syndrome derived cancers. Proteins like MLH1/PMS2 together are commonly deficient in case of endometrial or colorectal cancer (mismatch repair) whereas MLH1, PMS2, MSH2 or MSH6 could also lack their expression. At the same time, upper tract cancers manifest a dual loss of MSH2 and MSH6 or pure MSH6 loss where the expression of MLH1 and PMS2 remain constant.

Researchers were confused because of variable effects of mismatch repair gene expressions in upper tract urothelial carcinoma so they wanted to know whether screening is effective for patients. Halen Cathro suggests Immunohistochemical testing for such patients that can be proceeded by molecular testing in case of positive results. Personal or family history of cancer cannot provide any help in case of upper tract urothelical carcinoma.

Cathro along her colleagues reviewed tissue samples of 117 patients with upper tract urothelial carcinoma and 160 patients with urothelial carcinoma. 1% of patients with bladder urothelial carcinoma and 9% of patients with upper tract urothelial carcinoma demonstrated mismatch repair protein loss. 40% with upper tract urothelial carcinoma and zero percent with bladder urothelial carcinoma were microsatellite instability-high. Research indicated that Lynch syndrome is present in the 1-3% of the upper tract and 2-6% of endometrial or colorectal cancer patients.

All the work done on Lynch syndrome indicates the importance of genetic testing and counseling for all members of the family. If microsatellite stability status of all such patients is recognized then further improvement can be made.

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