N47: Prevalence Of Mismatch Repair Deficiency In Small Bowel Carcinomas And Neuroendocrine Tumours

M. Suerink1, H. Hristova1, L. Sensuk1, S. ten Broeke1, E. Ahsmann2, C. Jansen3, C. Wauters4, C. van der Post5, A. Farina Sarasqueta6, H. Morreau6, M. Nielsen1

1 – Department of clinical genetics, LUMC, Leiden, The Netherlands. 2 – Department of pathology, Groene Hart hospital, Gouda, The Netherlands. 3 – Laboratorium pathology Oost-Nederland, The Netherlands. 4 – Canisius-Wilhelmina ziekenhuis, Nijmegen, The Netherlands. 5 – Radboud University Medical Centre, Nijmegen, The Netherlands. 6 – Department of pathology, LUMC, Leiden, The Netherlands.


Aim: Mismatch repair (MMR) deficiency in tumours is caused by biallelic loss of one of the MMR genes. Carriers of a heterozygous germline mutation in an MMR gene have Lynch syndrome and consequently a ~4% lifetime risk of developing small bowel cancer. Previous studies on prevalence of MMR deficiency in small bowel cancer have shown varying results, likely due to small sample size and differences in selection criteria. We aimed at establishing MMR deficiency prevalence in a large, unbiased cohort of small bowel cancers.

Method: A cohort of 308 (adeno)carcinomas and 43 neuroendocrine tumours was collected. MMR deficiency was analysed by performing immunohistochemical staining for PMS2 and MSH6.

Results: 16.9% of small bowel (adeno)carcinomas and 0% of neuroendocrine tumours was MMR deficient.

Conclusion: MMR deficiency prevalence of 16.9% is similar to that observed in colorectal cancers (CRC). ~3% of all CRC cases is caused by Lynch syndrome and universal screening of all CRC cases below age 70 for MMR deficiency is common in many countries. Similar MMR deficiency rates for small bowel cancers suggest similar Lynch prevalence. To further evaluate this, staining of MLH1 and MSH2 will be performed in the MMR deficient tumours and the MMR genes will be sequenced in tumour DNA.