Should you repeat mismatch repair testing in tumour recurrences? An evaluation of repeat mismatch repair testing by immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts.

Aird JJ1,2, Steel MJ1, Chow C3, Ho J4, Wolber R5, Gilks CB1,2, Hoang LN1,2, Schaeffer DF1,2.

Author information

1: Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
2: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
3: Genetic Pathology Evaluation Centre, Jack Bell Research Center, Vancouver, British Columbia, Canada.
4: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
5: Department of Laboratory Medicine and Pathology, Lions Gate Hospital, North Vancouver, BC, Canada.

Abstract

AIMS:

The role of mismatch repair (MMR) testing has evolved from identifying Lynch syndrome patients to predicting response to immune checkpoint inhibitors. This has led to requests from clinicians to retest recurrences of MMR proficient primary tumours in the hope that the recurrence may show a different MMR status and qualify the patient for treatment. We aimed to determine whether repeat testing is warranted.

METHODS AND RESULTS:

We evaluated recurrent tumours (local recurrences or metastases) from 137 patients with MMR proficient primary tumours of the gastrointestinal and gynaecological tracts. The local recurrences and metastases all occurred at least 30 days after resection of the primary tumour. We used a combination of a tissue microarray (TMA) and whole slide staining to perform immunohistochemistry (IHC) for PMS2, MLH1, MSH2 and MSH6 and compared the results to the MMR status of the primary tumour. 3/137 (2%) initially showed a discordant staining pattern. However, further investigation showed that these discordances were attributed to some of the known pitfalls associated with MMR IHC interpretation - post radiotherapy loss of MSH6 expression and subclonal loss of MLH1 staining. We did not identify any cases with a genuine discordance in MMR status.