Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Mod Pathol. 2013 Sep;26(9):1172-82. doi: 10.1038/modpathol.2013.64. Epub 2013 Apr 5.
MST1R (RON) and MET are receptor tyrosine kinase gene family members that form a noncovalent complex on the cell surface, a critical step in tumor progression. A recent study suggested a prognostic role of MET expression in Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL). The purpose of this study was to examine the prognostic significance of MET and MST1R expression in cHL. The prognostic impact of MET and MST1R was examined in 100 patients with cHL (median age: 32 years) by immunohistochemistry and mRNA in situ hybridization. The median follow-up time was 95 months (interquartile range: 42-126 months). MET or MST1R protein expression was associated with high MET or MST1R mRNA expression, respectively. Thirty-eight patients (38%) expressed MET protein in HRS cell, which was associated with better overall survival (P=0.004). Twenty-six patients (26%) expressed MST1R protein, which was associated with better overall survival (P=0.022) and event-free survival (P=0.021). Multivariate analysis identified MET protein as an independent prognostic factor for overall survival and MST1R protein as an independent prognostic factor for event-free survival. Subgroup analysis according to Ann Arbor stage showed that expressions of MET and MST1R protein have prognostic impact in the advanced stage only. In particular, coexpression of MST1R and MET protein was associated with a better survival outcome than MET or MST1R expression alone or no expression. This study suggests that MET and MST1R are independent prognostic factors in classical cHL, and may allow the identification of a subgroup of cHL patients who require more intensive therapy.
MST1R（RON）和 MET 是受体酪氨酸激酶基因家族成员，它们在细胞表面形成非共价复合物，这是肿瘤进展的关键步骤。最近的一项研究表明，MET 表达在经典霍奇金淋巴瘤（cHL）中的霍奇金/里德-斯特恩伯格（HRS）细胞中具有预后作用。本研究旨在探讨 MET 和 MST1R 表达在 cHL 中的预后意义。通过免疫组织化学和 mRNA 原位杂交技术，在 100 例 cHL 患者（中位年龄：32 岁）中检测了 MET 和 MST1R 的表达及其预后意义。中位随访时间为 95 个月（四分位距：42-126 个月）。MET 或 MST1R 蛋白表达分别与高 MET 或 MST1R mRNA 表达相关。38 例（38%）HRS 细胞表达 MET 蛋白，与总生存期（P=0.004）相关。26 例（26%）表达 MST1R 蛋白，与总生存期（P=0.022）和无事件生存期（P=0.021）相关。多变量分析显示 MET 蛋白是总生存期的独立预后因素，MST1R 蛋白是无事件生存期的独立预后因素。根据 Ann Arbor 分期的亚组分析表明，MET 和 MST1R 蛋白的表达仅在晚期具有预后意义。特别是，MST1R 和 MET 蛋白的共表达与单独表达 MET 或 MST1R 或不表达相比，与更好的生存结果相关。本研究表明，MET 和 MST1R 是经典 cHL 的独立预后因素，可能有助于确定需要更强化治疗的 cHL 患者亚组。
