domingo, 5 de agosto de 2018

Routine molecular analysis for Lynch syndrome among adenomas or colorectal cancer within a national screening program. - PubMed - NCBI

2018 Jul 28. pii: S0016-5085(18)34817-0. doi: 10.1053/j.gastro.2018.07.029. [Epub ahead of print]

Routine molecular analysis for Lynch syndrome among adenomas or colorectal cancer within a national screening program.

Goverde A1, Wagner A2, Bruno MJ3, Hofstra RMW2, Doukas M4, van der Weiden MM4, Dubbink HJ4, Dinjens WNM4, Spaander MCW5.

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Abstract

BACKGROUND & AIMS:

It is important to identify individuals with Lynch syndrome because surveillance programs can reduce their morbidity and mortality from colorectal cancer (CRC). We assessed the diagnostic yield of immunohistochemistry to detect Lynch syndrome in patients with advanced and multiple adenomas within our national CRC screening program.

METHODS:

We performed a prospective study of all participants (n=1101; 55% male; median age, 66 years; interquartile range, 61-70 years) referred to the Erasmus MC in The Netherlands after a positive result from a fecal immunohistochemical test, from December 2013 to December 2016. Colon tissues were collected from patients with advanced adenomas, ≥4 non-advanced adenomas, or CRC, and analyzed by immunohistochemistry to identify patients with loss of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, or PMS2)-a marker of Lynch syndrome. Specimens from patients with loss of MLH1 were analyzed for MLH1 promoter hypermethylation. Patients with a MMR-deficient tumor or adenoma without MLH1 promoter hypermethylation were referred for genetic analysis.

RESULTS:

At colonoscopy, 456 patients (41%) (65% male; mean age, 67 years; interquartile range, 63-71 years) were found to have CRC and/or an adenoma eligible for analysis by immunohistochemistry. Of 56 CRCs, 7 (13%) had lost an MMR protein and 5 had hypermethylation of the MLH1 promoter. Analyses of tumor DNA revealed that 2 patients without MLH1 promoter hypermethylation had developed sporadic tumors. In total, 400 patients with adenomas were analyzed. Of the examined adenomas, 208 (52%) had a villous component and/or high-grade dysplasia: 186 (47%) had a villous component and 41 (10%) had high-grade dysplasia. Only 1 adenoma had lost an MMR protein. This adenoma was found to have 2 somatic mutations in MSH6.

CONCLUSIONS:

In a CRC screening program in The Netherlands for individuals aged 55-75 years, routine screening for Lynch syndrome by immunohistochemistry analysis of colon tissues from patients with advanced and multiple adenomas identified no individuals with this genetic disorder.