叶酸受体α（FOLR1）阳性的高级别浆液性卵巢癌（HGSOC）的靶向治疗现在是铂类耐药疾病的支柱。然而，低级别浆液性卵巢癌 (LGSOC) 中 FOLR1 阳性率尚未得到充分记录。 LGSOC 比 HGSOC 不太常见，它往往对传统的铂类化疗方案反应不佳，特别是在复发时。因此，迫切需要确定可能有助于确定 LGSOC 更有效治疗方法的分子靶点。在这项工作中，我们评估了 FOLR1 阳性/阴性 LGSOC 与其高级对应物的基因组和转录组学景观。使用大型精密肿瘤学数据库，对 281 个 LGSOC 和 5086 个 HGSOC 的队列进行了下一代测序和免疫组织化学分析。根据 NGS 结果计算相关 MAPK 激活，并通过分子改变分层完成患者生存分析。与 LGSOC (24.6%) 相比，HGSOC 肿瘤的 FOLR1 状态患病率 (43.5%) 显着更高，PD-L1 状态显着更高。相反，与 HGSOC 相比，LGSOC 的 KRAS 和 NRAS 突变发生率较高，且 BRAF 突变几乎具有排他性。 FOLR1-LGSOC 和 HGSOC 的 T 细胞炎症肿瘤患病率相似，但 FOLR1 LGSOC 的 T 细胞炎症肿瘤患病率显着低于 FOLR1 HGSOC。与 HGSOC 相比，通过 MAPK 激活评分 (MPAS) 量化的 MAPK 激活在低级别肿瘤中显着较高，但 FOLR1 与 FOLR1-LGSOC 之间没有观察到差异。 - 级肿瘤为 FOLR1，表明 LGSOC 中的 FOLR1 表达可能是这种罕见组织学的可行靶点，特别是在复发情况下。版权所有 © 2024。由 Elsevier Inc. 出版。

Targeted therapy in folate receptor alpha (FOLR1)-positive high grade serous ovarian carcinoma (HGSOC) is now a mainstay for platinum-resistant disease. However, the rate of FOLR1-positivity in low grade serous ovarian carcinoma (LGSOC) is not well documented. Less common than HGSOC, LGSOC tends to respond poorly to traditional platinum-based chemotherapeutic regimens, particularly in recurrence. Thus, there is an urgent need to identify molecular targets that may assist in identifying more efficacious treatments for LGSOC. In this work, we assessed the genomic and transcriptomic landscapes in FOLR1-positive/negative LGSOC compared to its high-grade counterpart.Using a large precision oncology database, next-generation sequencing and immunohistochemistry was performed on a cohort of 281 LGSOC and 5086 HGSOC. Associated MAPK activation was calculated based on NGS results and patient survival analysis was completed stratified by molecular alteration.Compared with LGSOC (24.6 %), HGSOC tumors have significantly higher prevalence of FOLR1+ status (43.5 %) and significantly higher PD-L1+ status. Conversely, LGSOC had higher prevalence of KRAS and NRAS mutations, with a near exclusivity for BRAF mutation compared to HGSOC. FOLR1- LGSOC and HGSOC had similar prevalences of T cell-inflamed tumors, though FOLR1+ LGSOC had a significantly lower prevalence of T-Cell inflamed tumors than FOLR1+ HGSOC. MAPK activation, quantified via MAPK activation score (MPAS), was significantly higher in low-grade tumors compared to HGSOC, yet no difference between FOLR1+ vs FOLR1- LGSOC was observed.Though less than in high-grade disease, a notable portion of low-grade tumors were FOLR1+, suggesting FOLR1 expression in LGSOC could be a viable target for this rare histology, particularly in the recurrent setting.Copyright © 2024. Published by Elsevier Inc.