de Angelis de Carvalho Nathália, Niitsuma Bianca Naomi, Kozak Vanessa Nascimento, Costa Felipe D'almeida, de Macedo Mariana Petaccia, Kupper Bruna Elisa Catin, Silva Maria Letícia Gobo, Formiga Maria Nirvana, Volc Sahlua Miguel, Aguiar Junior Samuel, Palmero Edenir Inez, Casali-da-Rocha José Cláudio, Carraro Dirce Maria, Torrezan Giovana Tardin
Genomics and Molecular Biology Group, International Research Center/CIPE, A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil.
Oncogenetics Service, Hospital Erasto Gaertner, Curitiba 81520-060, Brazil.
Cancers (Basel). 2020 Jul 9;12(7):1848. doi: 10.3390/cancers12071848.
Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 carriers and 2 ), with 2 having Muir-Torre phenotypes. For two carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.
林奇综合征（LS）是一种遗传性癌症易感综合征，最常与上皮性肿瘤相关，尤其是结直肠癌（CRC）和子宫内膜癌（EC）。本研究的目的是通过对同时出现肉瘤和LS谱系肿瘤的患者进行临床和分子特征分析，探讨肉瘤与LS之间的关系。我们确定了27例被诊断为CRC、EC和其他LS相关肿瘤的患者，他们在同一个体或家族中患有肉瘤。进行了种系基因检测、错配修复（MMR）蛋白免疫组化、微卫星不稳定性（MSI）和其他分子分析。确定了5例有肉瘤个人或家族史的LS患者（3例携带者和2例 ），其中2例具有穆尔-托雷表型。对于2例携带者，我们证实了肉瘤（1例脂肪肉瘤和2例骨肉瘤）的病因与LS相关，因为这些肿瘤存在MSH2/MSH6缺陷、MSI高或出现截短的MSH2转录本。此外，我们回顾了之前43篇关于LS患者肉瘤的报道，这些报道显示 改变的频率很高（58%）。总之，肉瘤是LS患者中一种罕见的临床表现，尤其是在 携带者中，对肿瘤生物学特征的分析有助于确定肿瘤病因和新的治疗选择。
