AI Article Synopsis
- The study focuses on a rare pattern of mismatch repair protein deficiencies in colorectal and endometrial cancers, specifically the loss of PMS2 and MSH6 proteins while MLH1 and MSH2 remain intact.
- It found this abnormality in 1.9% of colorectal cancers examined and identified specific mutations in PMS2 and MSH6 through Next Generation Sequencing (NGS).
- The research suggests incorporating NGS into Lynch syndrome screening protocols to better identify somatic mutations in cases where immunohistochemistry results are unclear.
Article Abstract
Background: Immunohistochemistry (IHQ) is commonly used for the detection of mismatch repair proteins deficiency (MMRD). One very infrequent abnormal pattern of MMR protein expression is the loss of PMS2 and MSH6, with intact expression of MLH1 and MSH2.
Case Presentation: We review the frequency of this MMRD IHC pattern among 108 colorectal (CRCs) and 35 endometrial cancers in our files with loss of expression of at least one protein, and present two CRCs showing loss of PMS2 and MSH6 protein expression (1.9% of CRCs). NGS analysis of these tumours identified PMS2 mutations (R134* germline mutation in one tumour and M1R and c.1239delA somatic mutation in the other) as the primary event and somatic MSH6 mutation (c.3261dupC) as the secondary event in both tumours.
Conclusions: This study suggests that Next Generation Sequencing (NGS) tumour analysis should be considered in the algorithm of Lynch syndrome screening to detect MMR gen somatic mutation in inconclusive cases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362514 | PMC |
| http://dx.doi.org/10.1186/s13000-020-01001-2 | DOI Listing |
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