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
| Autor: | Andrew J Wallace, David J. Kerr, Kelly Handley, Richard Gray, Phil Quirke, Laura Magill, Gordon G A Hutchins, James Hill, Paul J. Barrow, D. Gareth Evans, Susan D. Richman |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Histology beta2‐microglobulin (B2M) Colorectal cancer colorectal cancer QUASAR medicine.disease_cause pMMR DNA Mismatch Repair Pathology and Forensic Medicine Frameshift mutation 03 medical and health sciences 0302 clinical medicine Internal medicine dMMR medicine Humans Missense mutation Stage (cooking) Beta2-Microglobulin (B2M) Aged Mutation business.industry Beta-2 microglobulin Mismatch-repair Original Articles General Medicine Middle Aged medicine.disease mismatch‐repair 030104 developmental biology 030220 oncology & carcinogenesis Immunohistochemistry Original Article Female DNA mismatch repair Neoplasm Recurrence Local Colorectal Neoplasms beta 2-Microglobulin business |
| Zdroj: | Histopathology Barrow, P, Richman, S D, Wallace, A, Handley, K, Hutchins, G G A, Kerr, D, Magill, L, Evans, D G, Gray, R, Quirke, P & Hill, J 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 . https://doi.org/10.1111/his.13895 |
| ISSN: | 0309-0167 |
| DOI: | 10.1111/his.13895 |
| Popis: | 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:Of 121 dMMR CRCs, deleterious B2M mutations were detected in 39 (32%). Five tumours contained missense B2M-variants of unknown significance, and were thus excluded from further analyses, leaving 116 dMMR tumours. 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 |
| Databáze: | OpenAIRE |
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