Application and timing of MMR IHC in tumours of patients with advanced cancer

Cathryn Moss1, Elena Cojocaru1, Simon Ward1, Janet Hanwell1, Wen Xu1,2, Mary van Zyl1, Lorraine O’Leary1, Johann de Bono1,2, Udai Banerji1,2, Stan Kaye1,2, Anna Minchom1,2, Angela George1, Juanita Lopez1,2, Terri McVeigh1

1Royal Marsden NHS Foundation Trust , London, United Kingdom. 2Institute of Cancer Research , London, United Kingdom

Abstract

Background and objectives 

Lynch Syndrome is an under-recognised, high-risk cancer predisposition syndrome associated with MMR deficiency. Since February 2017, universal tumour-based mismatch repair(MMR) immunohistochemistry(IHC) has been recommended for all patients with colorectal cancer[1], and suggested for patients with endometrial, ureteric or non-serous ovarian malignancies[2][3][4][5]. The aim of this study was to examine application and timing of MMR-IHC in a sample of patients with advanced cancer.

Methods 

A retrospective review of patients with advanced cancer referred from the Drug Development Unit to the Cancer Genetics Unit over a 42 month period was undertaken, and data regarding patient and tumour characteristics, family history, tumour MMR-IHC and germline investigations obtained by chart review.

Results 

Ninety-one patients were referred from DDU to CGU over 42 months; seventeen with personal and/or family histories suspicious for Lynch syndrome. The average age at diagnosis of those where LS was suspected was 45±16(29-65) years. The median interval between diagnosis and MMR-IHC was 2 years(0-8). Five patients had uninformative germline MMR gene testing.

Conclusions 

This study demonstrates some delays in undertaking investigations for Lynch Syndrome even in patient under continuous medical care for advanced or relapsing cancer, with suspicious personal or family histories.  Identification of MMR-deficiency may prompt germline investigations with potentially serious implications for the patient and their family, but may also have implications for treatment/trial eligibility, particularly for advanced cases where standard options are limited.

 

Abstract references

[1] NICE Guidance : Molecular testing strategies for Lynch syndrome in people with colorectal cancer  [DG27] , 2017 (https://www.nice.org.uk/guidance/dg27/chapter/1-Recommendations)

[2] Watkins JC, Yang EJ, Muto MG, Feltmate CM, Berkowitz RS, Horowitz NS, et al. Universal screening for mismatch-repair deficiency in endometrial cancers to identify patients with Lynch syndrome and lynch-like syndrome. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 2017;36(2):115e27.

[3] Ju JY, Mills AM, Mahadevan MS, Fan J, Culp SH, Thomas MH, et al. Universal Lynch syndrome screening should be performed in all upper tract urothelial carcinomas. Am J Surg Pathol 2018; 42(11):1549e55.

[4] Ryan NAJ, Blake D, Cabrera-Dandy M, Glaire MA, Evans DG, Crosbie EJ. The prevalence of Lynch syndrome in women with endometrial cancer: a systematic review protocol. Syst Rev. 2018;7(1):121. Published 2018 Aug 16. doi:10.1186/s13643-018-0792-8

[5] Scaranti, M, Murali, K, Orbegoso Aguilar, C, George, A. Prevalence and clinical implications of mismatch repair (MMR) deficiency in unselected non-serous epithelial ovarian cancer (EOC) patients (pts), Journal of Clinical Oncology, 2019 37(15_suppl):1521-1521

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