Sanmamed Miguel F, Esteban E, Uriol E, Zarate R, Capelan M, Muriel C, Crespo G, Berros J P, Pardo-Coto P, Perez Q, Alvarez-Fernández C, Jiménez Fonseca P, Luque M, Astudillo A
Department of Immunobiology, School of Medicine, Yale University, 300 George Street, Suite 203A, New Haven, CT, 06511, USA.
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
J Transl Med. 2017 Mar 20;15(1):62. doi: 10.1186/s12967-017-1162-3.
Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT.
Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays.
Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3-9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations.
Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT.
腹股沟睾丸切除术对70 - 80%的临床I期睾丸生殖细胞肿瘤（CS I TGCT）具有治愈作用。识别复发风险低的患者对于避免不必要的治疗至关重要。本研究的目的是探讨表皮生长因子受体（EGFR）、人错配修复蛋白1/人错配修复蛋白2（hMLH-1/hMSH-2）和微卫星不稳定性（MSI）作为CS I TGCT复发的潜在预后因素。
本研究纳入了56例行腹股沟睾丸切除术的CS I TGCT患者。我们分析了临床病理因素和分子因素与生存之间的关系。通过免疫组织化学分析hMLH1、hMSH2和EGFR的表达。在选定病例中通过焦磷酸测序分析确定hMLH1启动子的甲基化状态。通过PCR标记片段分析EGFR外显子19、20、21，并使用标准多重MSI检测确定MSI状态。
经典病理因素，如淋巴管浸润、胚胎癌比例高、睾丸网浸润或肿瘤大小≥4 cm与较高的复发风险显著相关。此外，发现附睾浸润被证明是复发的一个显著独立不良预后因素（p = 0.001）。hMLH1或hMSH2表达与复发风险无显著关联，未发现MSI。30.4%的样本中观察到EGFR表达，其表达与较高的复发风险相关（风险比3.5；95%置信区间1.3 - 9.8；p = 0.016）。所有病例均未出现EGFR激酶结构域突变。
附睾浸润和EGFR表达，而非hMLH-1/hMSH-2或MSI，可能作为CS I TGCT复发的新预后因素。
