mismatch repair immunohistochemical patterns

Universal screening for Lynch syndrome through mismatch repair (MMR) immunohistochemistry (IHC) on tumor samples has brought to light several heterogenous MMR staining patterns.

Colorectal adenocarcinoma

 Universal testing for all patients with colorectal adenocarcinoma age 70 or younger.

 Testing surgical resection or biopsy specimen using IHC, PCR and/or both.

 For loss of MLH1 protein expression, perform MLH1 hypermethylation and/or BRAF V600E mutation analysis to determine Lynch / HNPCC vs sporadic.

 If loss of MSH2, MSH6, PMS2 or methylation/ BRAF V600E negative loss of MLH1 refer for possible genetic counseling.

Endometrial carcinomas

 Discrete subclonal loss of MMR protein expression occurs in up to 7.2% of EC and, in our experience, only in endometrioid components.

 Importantly, subclonal MLH1 MMR defects appear to be a biological phenomenon that can be explained by methylation and somatic events, without evidence of underlying germline alterations.

 In mixed tumors, subclonal or total MMR IHC deficiency was confined to endometrioid components.

References

 Unusual Mismatch Repair Immunohistochemical Patterns in Endometrial Carcinoma. Watkins JC, Nucci MR, Ritterhouse LL, Howitt BE, Sholl LM. Am J Surg Pathol. 2016 May 16. PMID: 27186853