Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Gynecol Oncol. 2023 Sep;176:115-121. doi: 10.1016/j.ygyno.2023.07.010. Epub 2023 Jul 26.
Folate receptor alpha (FRα), which is expressed in various cancers, is a potential therapeutic target. However, its expression and clinical significance in uterine (UCS) and ovarian carcinosarcoma (OCS) remain to be elucidated.
This retrospective study included patients with gynecologic carcinosarcoma who underwent primary surgery between 1997 and 2019 at our institution. Immunohistochemical staining of surgical FFPE specimens was performed for FRα and HER2. FRα was evaluated using the H-score and the 4-tired scoring system (0 to 3+). Subsequently, FRα expression (≥5% of tumor cells with ≥1+ intensity) and FRα-high (score 2+ and 3+) were evaluated. HER2 was scored according to the modified ASCO/CAP criteria. The association between FRα-high and clinicopathological features, HER2 expression, and survival was assessed in UCS.
A total of 120 patients with UCS and nine patients with OCS were included. In UCS, FRα expression was observed in all patients, whereas FRα-high status was present in 20% of patients. Among HER2-negative UCS, 34% exhibited FRα-high. No significant association was observed between clinicopathological characteristics and FRα status. During the follow-up period (median 34.5 mo), FRα-high was not strongly associated with progression, free survival, and overall survival. All the OCS tumor specimens showed FRα-high expression.
FRα expression was observed in all the UCS and OCS specimens, including HER2-negative UCS patients. This widespread FRα expression suggests that FRα-targeted therapies may hold promise for the treatment for gynecologic carcinosarcoma. However, in uterine carcinosarcoma, no significant relationship was observed between FRα expression and clinicopathological features or prognosis.
叶酸受体 α（FRα）在多种癌症中表达，是潜在的治疗靶点。然而，其在子宫（UCS）和卵巢癌肉瘤（OCS）中的表达及其临床意义仍需阐明。
本回顾性研究纳入了 1997 年至 2019 年期间在我院接受初次手术治疗的妇科癌肉瘤患者。对手术 FFPE 标本进行 FRα 和 HER2 的免疫组织化学染色。采用 H 评分和 4 级评分系统（0 至 3+）评估 FRα。随后，评估 FRα 表达（≥1+强度的肿瘤细胞中≥5%）和 FRα 高（评分 2+和 3+）。HER2 根据改良 ASCO/CAP 标准进行评分。评估 FRα 高与 UCS 的临床病理特征、HER2 表达和生存之间的关系。
共纳入 120 例 UCS 患者和 9 例 OCS 患者。在 UCS 中，所有患者均有 FRα 表达，而 FRα 高的比例为 20%。在 HER2 阴性的 UCS 中，34%的患者 FRα 高。FRα 状态与临床病理特征无显著相关性。在随访期间（中位随访时间 34.5 个月），FRα 高与进展、无进展生存期和总生存期均无明显相关性。所有 OCS 肿瘤标本均表现为 FRα 高表达。
所有 UCS 和 OCS 标本均有 FRα 表达，包括 HER2 阴性的 UCS 患者。这种广泛的 FRα 表达提示 FRα 靶向治疗可能为妇科癌肉瘤的治疗带来希望。然而，在子宫癌肉瘤中，FRα 表达与临床病理特征或预后无显著相关性。
