Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.
Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.
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DOI：
10.1016/j.tranon.2017.01.014
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发表时间：
2017-06
影响因子：
5
通讯作者：
Ford CE
中科院分区：
文献类型：
--
作者：
Henry CE;Emmanuel C;Lambie N;Loo C;Kan B;Kennedy CJ;de Fazio A;Hacker NF;Ford CE
目的：ROR 1和ROR 2受体酪氨酸激酶均与卵巢癌进展有关，并已显示驱动迁移和侵袭。基质在卵巢癌转移中的作用越来越重要;然而，在同一临床队列中，肿瘤或基质细胞中的ROR 1和ROR 2表达均未进行分析。目的：确定ROR 1和ROR 2在卵巢癌和周围微环境中的表达，并检查与临床病理特征的相关性。方法：ROR 1和ROR 2的免疫组化用于评估上皮性卵巢癌患者队列（n = 178）中的受体表达。结果进行了分析，与临床和组织病理学特征和生存。正常、原发和转移性病灶的匹配患者样本病例研究用于检查ROR表达与卵巢癌进展的关系。结果：ROR 1和ROR 2在卵巢恶性上皮和间质中异常表达。ROR 2在早期、低级别类胶质瘤中表达较高。ROR 2基质表达在浆液性亚型中最高。在匹配的患者病例研究中，转移性样品在基质中具有更高的ROR 2表达，并且复发性样品在肿瘤和基质中具有最高的ROR 2表达。结论：ROR 1和ROR 2在卵巢癌的所有组织学亚型中的肿瘤相关基质中表达，并且具有作为可能破坏肿瘤和基质相互作用的治疗靶点的潜力。
OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.