P-250 - Clinical Impact and Cost Implication of Routine MMR Protein Immunohistochemistry in High Risk Dukes B Colon Cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Bioethics, Legal, and Economic Issues
Colon Cancer
Pathology/Molecular Biology
Presenter K. Chiu
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors K. Chiu, J. Chambers, I. Chandler, M. Osborne
  • Royal Devon and Exeter Hospital, Exeter/UK

Abstract

Introduction

dMMR (deficient MisMatch Repair) has been shown to be a prognostic marker for improved outcome in colon cancer patients1. There is also accumulating evidence that dMMR tumours may not derive benefit from fluoropyrimidine-based chemotherapy2. The general consensus is that high risk Dukes B patients who have dMMR may not require adjuvant chemotherapy1,2.

MMR (DNA MisMatch Repair) status can either be determined by polymerase chain reaction analysis (PCR) or by immunohistochemistry (IHC) for MMR proteins (MLH1, MSH1, MSH6 and PMH2). The absence of immunohistochemical staining for one or more of these proteins implies dMMR1. Our centre has routinely been testing MMR status in high risk Dukes B colon cancer patients using MMR protein immunohistochemistry. The aim of this retrospective study was to assess the clinical impact and cost implication of IHC test.

Methods

Data of colon cancer patients tested for MMR status using IHC was collected from our histopathology department. Dukes B colon cancer patients who had one or more features of T4 primary tumour, poor differentiation, perforation, obstruction, lymphovascular or perineural invasions were considered to be high risk. Chemotherapy decisions for high risk Dukes B patients were gathered from the medical notes and MDT meeting minutes. The costs of MMR protein immunohistochemistry and adjuvant Capecitabine chemotherapy were analysed.

Results

41 colon cancer patients were tested for MMR status using immunohistochemistry between March 2013 and October 2014 (18 months). 31 of the 41 patients were resected high risk Dukes B colon cancer patients. 24 of the 31 patients (77%) were under the age of 75 and were considered for adjuvant chemotherapy. 3 of the 24 patients (13%) were found to have dMMR. 2 of the 3 dMMR patients did not proceed to have adjuvant treatment. 13 of the 24 patients (54%), including 1 dMMR patient, were commenced on adjuvant chemotherapy.

7 of the 31 high risk Dukes B patients (23%) were over the age of 75. None of the over-75 patients were given chemotherapy. 4 of them (57%) were found to have dMMR. All dMMR patients had right sided colon cancer.

The overall prevalence of dMMR in high risk Dukes B patients was 23%. The cost of an MMR protein immunohistochemistry was under £50, whereas a 6 month course of Capecitabine chemotherapy, including all non-drug clinical costs, could amount up to £3500.

The other 10 patients tested in-house for MMR status were patients of different stages of colon carcinoma ie Dukes A, C, D and non-high risk B. They were selectively tested for various clinical reasons.

Conclusion

As a practice locally, dMMR is increasingly becoming an important factor in deciding against adjuvant chemotherapy. This study allowed us to support routine MMR protein immunohistochemistry in high risk Dukes B patients. In order to improve clinical efficiency and cost, changes have been made to MMR test patients who are fit and eligible for chemotherapy.