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- Title
Dépistage du syndrome de Lynch chez les patientes atteintes d'un carcinome de l'endomètre: un panel immunohistochimique à deux anticorps (PMS2/MSH6) pourrait contribuer au sous-diagnostic des tumeurs déficientes en MSH2.
- Authors
Wood, Richard K.; Offman, Saul L.; Murray, Shawn K.; Carter, Michael D.
- Abstract
Lynch syndrome is an inherited condition of defective DNA mismatch repair (MMR), leading to an increased lifetime risk of cancer at multiple sites. Screening for Lynch syndrome is now recommended for all cases of newly diagnosed endometrial cancer using either two-(PMS2, MSH6) or four-antibody (PMS2, MSH6, MSH2, MLH1) immunohistochemical (IHC) panels. Recent studies have indicated that twoantibody testing may lead to under-diagnosis of MSH2-deficient tumours in cases where MSH6 staining is weak or focal, potentially leading to under-diagnosis of Lynch syndrome. We conducted a retrospective analysis of 293 cases of endometrial carcinoma diagnosed at our hospital between 2016 and 2019. Cases were initially screened using the two-antibody panel, expanding to four antibodies when PMS2 or MSH6 expression was lost. For our study, MSH6 expression was reviewed; if weak, focal, or both, MSH2 IHC was performed. When a previously undetected loss of MSH2 expression was found, the attending clinician was informed to arrange referral to Medical Genetics. Overall, 68 of 293 tumours (23.2%) were MMRdeficient; 54 showing loss of MLH1/PMS2 (18.4%), 1 with MSH2/MSH6 loss (0.3%), 2 with isolated PMS2 loss (0.7%), 4 with isolated MSH6 loss (1.4%), and 6 with isolated MSH2 loss (i.e. with intact MSH6; 2.0%). One tumour (0.3%) demonstrated loss of MSH6, MLH1 and PMS2. Two tumours (0.7%) with isolated MSH2 loss were previously unrecognized as MMR-deficient and hence at high risk for Lynch syndrome; one patient declined Medical Genetics referral and the other, upon negative germline testing, was found to have two somatic MSH2 mutations by tumour next-generation sequencing. The pattern of "intact" but weak/focal MSH6 with loss of MSH2 was seen in both biopsy and hysterectomy specimens in all six cases. This study identifies the frequency of MMR-deficient endometrial carcinomas in Atlantic Canada, highlights a potential pitfall of using two-antibody IHC screening for Lynch syndrome, and supports emerging recommendations for universal Lynch syndrome screening in endometrial cancer.
- Subjects
HEREDITARY nonpolyposis colorectal cancer; CANCER diagnosis; IMMUNOHISTOCHEMISTRY; DNA mismatch repair; MEDICAL screening
- Publication
Canadian Journal of Pathology, 2021, Vol 13, Issue 3, p14
- ISSN
1918-915X
- Publication type
Article