Fumagalli Caterina, Betella Ilaria, Rappa Alessandra, di Giminiani Maria, Gaiano Michela, De Vitis Luigi Antonio, Zambetti Benedetta, Vacirca Davide, Multinu Francesco, Venetis Konstantinos, Colombo Nicoletta, Barberis Massimo, Guerini Rocco Elena
Clinical Unit of Oncogenomics, European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy.
Department of Diagnostic Services, Division of Pathology, Azienda Socio Sanitaria Territoriale (ASST) Valle Olona, 21013 Gallarate, Italy.
Cancers (Basel). 2022 Mar 23;14(7):1638. doi: 10.3390/cancers14071638.
The establishment of PARP inhibitors in the treatment of epithelial ovarian carcinoma (EOC) has prompt BRCA assessment at the time of diagnosis. We described our five years of experience of tumor BRCA testing, as part of a multidisciplinary workflow for the management of EOC patients. We used a BRCA next-generation sequencing (NGS) test for profiling formalin-fixed, paraffin-embedded (FFPE) EOCs of 762 consecutive patients, with a success rate of 99.7% and a median turnaround time of 12 days. We found 178 (23.4%) cases with pathogenic/likely pathogenic (P/LP) mutations, 74 (9.7%) cases with variants of uncertain significance and 508 (66.8%) wild type tumors. Among 174 patients without P/LP mutations and investigated with multiple-ligation probe-amplification analysis on peripheral blood, two (1.1%) were positive for large rearrangements. Patients with P/LP alterations and/or with positive family history were referred to genetic counselling. Comparing tumor and blood NGS test results of 256 patients, we obtained a tumor test negative predictive value of 100% and we defined 76% of P/LP alterations as germline and 24% as somatic variants. The proposed workflow may successfully identify EOC patients with BRCA1/2 alteration, guiding both therapeutic and risk assessment clinical decisions.
PARP抑制剂在治疗上皮性卵巢癌（EOC）中的应用促使人们在诊断时进行BRCA评估。我们描述了我们在肿瘤BRCA检测方面的五年经验，这是EOC患者多学科管理工作流程的一部分。我们使用BRCA二代测序（NGS）检测对762例连续患者的福尔马林固定、石蜡包埋（FFPE）EOC进行分析，成功率为99.7%，中位周转时间为12天。我们发现178例（23.4%）病例存在致病/可能致病（P/LP）突变，74例（9.7%）病例存在意义未明的变异，508例（66.8%）为野生型肿瘤。在174例无P/LP突变且接受外周血多重连接探针扩增分析的患者中，2例（1.1%）存在大片段重排阳性。存在P/LP改变和/或家族史阳性的患者被转诊至遗传咨询。比较256例患者的肿瘤和血液NGS检测结果，我们获得的肿瘤检测阴性预测值为100%，我们将76%的P/LP改变定义为种系变异，24%为体细胞变异。所提出的工作流程可能成功识别出存在BRCA1/2改变的EOC患者，指导治疗和风险评估的临床决策。
