Renal cell cancer linked to Lynch syndrome: Increased incidence and loss of mismatch repair protein expression

2016 ◽  
Vol 23 (6) ◽  
pp. 528-529 ◽  
Author(s):  
Christina Therkildsen ◽  
Patrick Joost ◽  
Lars Joachim Lindberg ◽  
Steen Ladelund ◽  
Lars Smith-Hansen ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Repair Protein ◽  
Mismatch Repair Protein

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry

2021 ◽  
pp. ijgc-2020-002299
Author(s):  
Surabhi Gupta ◽  
Cassandra B Nichols ◽  
Jessica Phillips ◽  
Sarah O'Sullivan ◽  
Chloe Ayres ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Western Australia ◽  
Universal Screening ◽  
Tumor Board ◽  
Repair Protein ◽  
Endometrial Carcinomas ◽  
Genetic Assessment ◽  
Mismatch Repair Protein

BackgroundIn 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia.ObjectiveTo compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment.MethodsA cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing.ResultsBetween 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years.ConclusionsUniversal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

scholarly journals Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome

2018 ◽  
Vol 33 (4) ◽  
pp. 534-539 ◽  
Author(s):  
Filomena Cariola ◽  
Vittoria Disciglio ◽  
Anna M. Valentini ◽  
Claudio Lotesoriere ◽  
Candida Fasano ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Splice Site ◽  
Pathogenic Role ◽  
Repair Protein ◽  
Tumor Tissues ◽  
Mismatch Repair Protein

Introduction: Lynch syndrome is caused by germline mutations in one of the mismatch repair genes ( MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. Case Description: Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. Conclusions: We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2).

scholarly journals DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression

EBioMedicine ◽  
2019 ◽  
Vol 39 ◽  
pp. 280-291 ◽  
Author(s):  
Satu Mäki-Nevala ◽  
Satu Valo ◽  
Ari Ristimäki ◽  
Virinder Sarhadi ◽  
Sakari Knuutila ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lynch Syndrome ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Somatic Mutations ◽  
Repair Protein ◽  
Mismatch Repair Protein

Mismatch Repair Protein Expression in Fordyce Granules

2017 ◽  
Vol 25 (3) ◽  
pp. 209-212 ◽  
Author(s):  
Angel Fernandez-Flores ◽  
José L. Rodríguez Peralto
Keyword(s):  
Protein Expression ◽  
Mismatch Repair ◽  
Repair Protein ◽  
Mismatch Repair Protein

Tissue-specific mismatch repair protein expression: MSH3 is higher than MSH6 in multiple mouse tissues

DNA Repair ◽  
2013 ◽  
Vol 12 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Stéphanie Tomé ◽  
Jodie P. Simard ◽  
Meghan M. Slean ◽  
Ian Holt ◽  
Glenn E. Morris ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mismatch Repair ◽  
Tissue Specific ◽  
Repair Protein ◽  
Mouse Tissues ◽  
Mismatch Repair Protein
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