Schoenfield Lynn, Janse Sarah, Kline David, Aronow Mary E, Singh Arun D, Craven Caroline, Abdel-Rahman Mohamed, Cebulla Colleen M
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Ocul Oncol Pathol. 2021 Sep;7(4):303-310. doi: 10.1159/000512174. Epub 2021 May 7.
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.
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.
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.
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 and gene expression was identified in a subset of UM tumors with poor genetic prognostic features.
Potentially actionable ER expression is present in greater than half of UM cases by IHC. Gene expression of and 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.
转移性葡萄膜黑色素瘤（UM）尚无有效治疗方法。迄今为止，尚无出版物报道UM中雌激素受体（ER）的免疫组化证据；然而，乳腺癌中ER病理报告的变化促使对UM中的ER进行重新检查，因为它可能代表一个潜在的治疗靶点。
使用当前乳腺癌的方法通过免疫组化（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。
对两个队列进行了一项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。还对癌症基因组图谱计划（TCGA）的80例患者的UM数据集进行了分析。
在CC队列中，34例可分析病例中有20例（59%）通过IHC检测到ER存在。在OSU队列的50例患者中，来自47例患者的52份标本足以进行分析。在这47例病例中，29例（62%）的肿瘤在≥1%的细胞核中ER呈阳性。在第二个队列中，阳性分为阳性（≥10%细胞核，34%病例）或低阳性（1-9%细胞核，28%病例）。在5例患者中，有配对样本，即原发性肿瘤和随后的复发或转移，5例中有4例ER一致。在TCGA数据库中，在具有不良遗传预后特征的一部分UM肿瘤中鉴定出 和 基因表达升高。
通过IHC检测，超过一半的UM病例中存在潜在可操作的ER表达。在具有不良预后特征的一部分UM肿瘤中， 和 的基因表达升高。这些数据为评估ER作为UM潜在治疗靶点提供了理论依据。
