Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome
| Autor: | Lisa Elze, Rachel S van der Post, Janet R Vos, Arjen R Mensenkamp, Mirjam S C de Hullu, Iris D Nagtegaal, Nicoline Hoogerbrugge, Richarda M de Voer, Marjolijn J L Ligtenberg |
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| Rok vydání: | 2023 |
| Předmět: |
Cancer Research
Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] All institutes and research themes of the Radboud University Medical Center Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] Oncology Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] |
| Zdroj: | Journal of the National Cancer Institute, 115, 7, pp. 853-860 |
| DOI: | 10.1093/jnci/djad063 |
| Popis: | Background Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics. Methods We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types. MSI status, somatic second hit alterations, and immunohistochemistry-based MMR status were analyzed in 236 noncolorectal and nonendometrial malignant tumors. Results In individuals with Lynch syndrome MSI-H/dMMR occurred both in Lynch-spectrum and in non–Lynch-spectrum malignancies (85% vs 37%, P Conclusions In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered. Moreover, Lynch syndrome should be considered an underlying cause of all MSI-H/dMMR malignancies other than colorectal and endometrial carcinomas. |
| Databáze: | OpenAIRE |
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