Next generation sequencing to decipher concurrent loss of PMS2 and MSH6 in colorectal cancer

• Main Authors: Esther Moreno, Juan M. Rosa-Rosa, Tamara Caniego-Casas, Ignacio Ruz-Caracuel, Cristian Perna, Carmen Guillén, José Palacios
• Format: Article
• Language: English
• Published: BMC 2020-07-01
• Series: Diagnostic Pathology
• Subjects: Colorectal cancer; Mismatch repair deficiency; Lynch syndrome; NGS; Case report
• Online Access: http://link.springer.com/article/10.1186/s13000-020-01001-2
• ISSN: 1746-1596

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.