Background: Metastatic uveal melanoma (UM) has no effective treatment. To date, no publications have reported immunohistochemical evidence of estrogen receptors (ERs) in UM; however, changes in pathologic reporting for ER in breast carcinoma prompted a re-examination of ER in UM, as it could represent a potential therapeutic target. Objective: To determine if UM tumors express ER by immunohistochemistry (IHC) using current methodology for breast cancer and to evaluate ER gene expression using a publicly available UM database. Methods: A retrospective IHC analysis with clinical correlation was performed on 2 cohorts: 57 cases from the Cleveland Clinic (CC) and 50 from the Ohio State University Wexner Medical Center (OSUWMC). Analysis of The Cancer Genome Atlas Project (TCGA) UM Dataset of 80 patients was also performed. Results: Presence of ER was detected by IHC in 20 of 34 (59%) analyzable cases in the CC cohort. Of the 50 patients in the OSU cohort, 52 specimens from 47 patients were sufficient for analysis. Of these 47 cases, 29 (62%) had tumor that was ER positive in ≥1% nuclei. In the second cohort, positivity was classified as positive (≥10% nuclei, 34% cases) or low positive (1–9% nuclei, 28% cases). In 5 patients, there were paired samples, that is, primary tumor and subsequent recurrence or metastasis, with concordance for ER in 4 of 5 cases. In the TCGA database, elevated ESR1 and ESR2 gene expression was identified in a subset of UM tumors with poor genetic prognostic features. Conclusions and Relevance: Potentially actionable ER expression is present in greater than half of UM cases by IHC. Gene expression of ESR1 and ESR2 was elevated in a subset of UM tumors with poor prognostic features. These data provide a rationale to evaluate ER as a potential target for therapy in UM.
Ocul Oncol Pathol

中文翻译：

---

雌激素受体在葡萄膜黑色素瘤中表达：治疗的潜在目标

背景：转移性葡萄膜黑色素瘤（UM）没有有效的治疗方法。迄今为止，没有出版物报道 UM 中雌激素受体 (ER) 的免疫组织化学证据；然而，乳腺癌 ER 病理报告的变化促使重新检查 UM 中的 ER，因为它可能代表一个潜在的治疗靶点。目的：使用当前的乳腺癌方法通过免疫组织化学 (IHC) 确定 UM 肿瘤是否表达 ER，并使用公开可用的 UM 数据库评估 ER 基因表达。方法：对 2 个队列进行了具有临床相关性的回顾性 IHC 分析：来自克利夫兰诊所 (CC) 的 57 例病例和来自俄亥俄州立大学韦克斯纳医学中心 (OSUWMC) 的 50 例病例。还对 80 名患者的癌症基因组图谱计划 (TCGA) UM 数据集进行了分析。结果：IHC 在 CC 队列的 34 例 (59%) 可分析病例中检测到 ER 的存在。在 OSU 队列的 50 名患者中，来自 47 名患者的 52 份样本足以进行分析。在这 47 例病例中，29 例 (62%) 的肿瘤在 ≥1% 的细胞核中呈 ER 阳性。在第二个队列中，阳性被分类为阳性（≥10% 细胞核，34% 病例）或低阳性（1-9% 细胞核，28% 病例）。在 5 名患者中，有配对样本，即原发肿瘤和随后的复发或转移，5 例中有 4 例符合 ER。在 TCGA 数据库中，在遗传预后特征较差的 UM 肿瘤子集中发现了升高的ESR1和ESR2基因表达。结论和相关性：IHC 在超过一半的 UM 病例中存在潜在可操作的 ER 表达。ESR1和ESR2的基因表达在具有不良预后特征的 UM 肿瘤子集中升高。这些数据为评估 ER 作为 UM 治疗的潜在目标提供了依据。
眼肿瘤病理