Barrow, P, Richman, SD orcid.org/0000-0003-3993-5041, Wallace, A et al. (8 more authors) (2019) Confirmation that somatic mutations of beta-2 microglobulin correlate with a lack of recurrence in a subset of stage II mismatch repair deficient colorectal cancers from the QUASAR trial. Histopathology, 75 (2). pp. 236-246. ISSN 0309-0167
Abstract
Aims: Beta2‐Microglobulin (B2M) forms part of the HLA class I complex and plays a role in metastatic biology. B2M mutations occur frequently in mismatch repair‐deficient colorectal cancer (dMMR CRC) with limited data suggesting they may protect against recurrence. Our experimental study tested this hypothesis by investigating B2M mutation status and B2M protein expression and recurrence in patients in the stage II QUASAR clinical trial.
Methods: Sanger sequencing was performed for the three coding exons of B2M on 121 dMMR and a subsample of 108 pMMR tumours; 52 with recurrence and 56 without. B2M protein expression was assessed by immunohistochemistry. Mutation status and protein expression were correlated with recurrence and compared to proficient mismatch repair (pMMR) CRCs.
Results: Deleterious B2M mutations were detected in 39/121 (32%) dMMR tumours. Five contained missense B2M‐variants of unknown significance, so were excluded from further analyses. With median follow‐up 7.4 years, none of the 39 B2M‐mutant tumours recurred, compared with 14/77 (18%) B2M‐wildtype tumours (p=0.005); six at local and eight at distant sites. Sensitivity and specificity of IHC in detecting B2M mutations was 87% and 71% respectively. Significantly (p<0.0001) fewer 3/104 (2.9%) of the 108 pMMR CRCs demonstrated deleterious B2M mutations. One pMMR tumour, containing a frameshift mutation, later recurred.
Conclusion: B2M mutations were detected in nearly one third of dMMR cancers, none of which recurred. B2M mutation status has potential clinical utility as a prognostic biomarker in stage II dMMR CRC. The mechanism of protection against recurrence and whether this protection extends to stage III disease remains unclear.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2019 The Authors. Histopathology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Beta2‐Microglobulin (B2M); colorectal cancer; QUASAR ; dMMR; pMMR; Mismatch‐repair |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L386 |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 May 2019 15:01 |
Last Modified: | 07 Jun 2023 13:58 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/his.13895 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145822 |
Downloads
Filename: Barrow_et_al-2019-Histopathology.pdf
Licence: CC-BY 4.0
Filename: S1.pdf
Licence: CC-BY 4.0
Filename: S2.pdf
Licence: CC-BY 4.0
Filename: S3.pdf
Licence: CC-BY 4.0