Pheochromocytoma is a relatively uncommon tumor, and the histomorphologic and biochemical features that may portend malignant behavior have poor overall consensus across various proposed classification systems. Steroid receptor coactivator-1 (SRC-1) is a nuclear protein that mediates transcriptional activity. Current diagnostic applications of SRC-1 are limited, and include distinguishing adrenocortical carcinoma (ACC) from renal cell carcinoma, and other mimickers. SRC-1 expression in pheochromocytoma has not been previously studied. Pheochromocytoma cases were retrieved from our Urological Pathology database and expert consultation files of the senior author, from 2015 to 2019. Clinicopathological data were obtained. SRC-1 expression was scored systematically. Thirty-eight cases were included, with a female predominance, and a mean age of 52 years (range, 16 to 75 y). Seven patients had heritable mutations including RET (n=3), VHL (2), SDHB (1), and ATM and PDGFRA (1). Two patients developed clinical metastasis, who individually had ATM and PDGFRA mutations, and SDHB p.V140F mutation. All heritable tumors were positive for SRC-1, including diffuse/strong staining and intensity in the VHL cases, and diffuse staining with variable intensity in RET cases. Diffuse positivity was seen in most of our heritable cases, providing evidence for a putative link between RET and downstream SRC-1 signaling. An inverse relationship was observed between SRC-1 expression and Pheochromocytoma of the Adrenal Gland Scaled Score/tumor size, suggesting that SRC-1 phenotype may become muted in pheochromocytomas that have malignant potential. SRC-1 expression in aggressive pheochromocytomas, may also be a potential diagnostic pitfall in view of the fact that these tumors may be misinterpreted as ACC in the primary or metastatic setting.

中文翻译：

---

Steroid Receptor Coactivator-1 在嗜铬细胞瘤中的表达

嗜铬细胞瘤是一种相对少见的肿瘤，可能预示恶性行为的组织形态学和生化特征在各种提议的分类系统中缺乏整体共识。类固醇受体辅激活因子-1 (SRC-1) 是一种介导转录活性的核蛋白。SRC-1 目前的诊断应用是有限的，包括区分肾上腺皮质癌 (ACC) 和肾细胞癌，以及其他类似物。先前尚未研究嗜铬细胞瘤中的 SRC-1 表达。从我们的泌尿病理学数据库和资深作者的专家咨询文件中检索 2015 年至 2019 年的嗜铬细胞瘤病例。获得了临床病理学数据。系统地对 SRC-1 表达进行评分。共纳入 38 例，以女性为主，平均年龄为 52 岁（范围 16 至 75 岁）。7 名患者具有遗传性突变，包括 RET (n=3)、VHL (2)、SDHB (1) 以及 ATM 和 PDGFRA (1)。两名患者出现临床转移，分别具有 ATM 和 PDGFRA 突变以及 SDHB p.V140F 突变。所有遗传性肿瘤均呈 SRC-1 阳性，包括 VHL 病例中的弥漫性/强染色和强度，以及 RET 病例中具有不同强度的弥漫性染色。在我们的大多数可遗传病例中都观察到了弥漫性阳性，为 RET 和下游 SRC-1 信号传导之间的假定联系提供了证据。观察到 SRC-1 表达与肾上腺标度评分/肿瘤大小的嗜铬细胞瘤之间呈负相关，表明 SRC-1 表型可能在具有恶性潜能的嗜铬细胞瘤中减弱。