Prevalence of mismatch repair deficiency and Lynch syndrome in small bowel carcinomas and neuroendocrine tumours

Manon Suerink, Gül Kilinc, Hristina Hristova, Lily Sensuk, Diantha Terlouw, Arantza Farina Saraqueta, Tom van Wezel, Hans Morreau, Maartje Nielsen

LUMC, Leiden, Netherlands


Previous estimates on prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer showed large variability, likely due to small sample size and differences in inclusion criteria. We aimed at establishing the prevalence of MMR deficiency and Lynch syndrome in a large and unbiased cohort of small bowel cancers.

A cohort of 387 small bowel (adeno)carcinomas and 61 neuroendocrine tumours was collected. MMR deficiency status was determined by immunohistochemically staining of the MMR proteins. Subsequent MLH1-promotor-hypermethylation analysis and next-generation sequencing (NGS) analysis of the MMR genes was used to determine the cause of MMR deficiency on a molecular level.

MMR deficiency was observed in 24.9% of resected small bowel (adeno)carcinomas and 5.2% in biopsies from carcinomas in the small bowel. MMR deficiency was 0% in the neuroendocrine tumours. Based on the first NGS results (as currently completed in 17 out of 47 MMR deficient tumours), the prevalence of Lynch syndrome in our cohort is  ≥1.3%. Analysis of the remaining samples will follow shortly and may increase this number to maximally 6.5%. Comparison of tumour and clinical characteristics will follow once NGS analysis is complete.

The MMR deficiency prevalence in small bowel (adeno)carcinomas is at least comparable to that observed in colorectal cancers. Similar MMR deficiency rates suggest similar Lynch syndrome prevalence and our (preliminary) results seem to support this.  Because of its relevance for treatment (PDL1-blockers) and family management, this indicates that all small bowel (adeno)carcinomas should be screened for MMR deficiency.