43例肢端型黑色素瘤MITF基因扩增分析及其临床意义

MITF gene amplification in 43 patients with acral melanoma and their clinical significance

目的黑色素瘤是侵袭性最强的恶性肿瘤之一，肢端黑色素瘤是黑色素瘤的一种特殊亚型，常见于亚洲黄种人群，发病机制尚不明确。小眼畸形相关转录因子（microphthalmia-associated transcription factor，MITF）是黑色素细胞生长、分化的重要调节蛋白，在黑色素瘤的发生、发展及转移过程中也发挥重要作用。本研究分析中国肢端型黑色素瘤患者MITF基因扩增情况及其临床意义。方法收集2010-01—01—2013—04—30北京肿瘤医院肾癌黑色素瘤内科43例中国肢端型黑色素瘤患者的石蜡包埋组织样本，应用实时定量PCR法检测MITF基因扩增情况，收集患者的临床病理资料进行统计分析。结果MITF基因在43例样本中的扩增率为48．8％（21／43）。MITF基因扩增和无扩增患者的年龄（Х^2=0．193，P=0．661）、性别（Х^2=0．587，P=0．443）、临床分期（Х^2=4．837，P=0．184）、血清LDH水平（Х^2=0．451，P=0．502）、溃疡（Х^2=0．910，P=0．340）、标本来源（Х^2=1．406，P：0．236）的差异均无统计学意义。但是，MITF基因扩增患者中肿瘤浸润厚度≥4mm比例为72．7％（8／11），明显高于无扩增患者的27．3％（3／12），差异有统计学意义（Fisher精确概率法，P=0．039）。MITF基因扩增和无扩增患者的中位总生存期分别为42．4个月（95％CI：29．7～55．1）和46．3个月（95％CI：34．5～58．2），差异无统计学意义，Х^2=0．287，P=0．592。结论中国肢端型黑色素瘤患者MITF基因扩增率较高，且扩增患者中肿瘤≥4mm比例显著高于无扩增患者，预示患者存在不良预后因素。

OBJECTIVE Melanoma is one of the most notoriously aggressive of human cancers. Acral lentiginous melanoma（ALM）is a special subtype which is found to be more commonly diagnosed in Asians. The pathogenesis is still not clear. Microphthalmia-associated transcription factor （MITF） acts as a master regulator of melanocyte development and differentiation and is also associated with melanoma development, progression and metastasis. This study was designed to investigate the frequency of MITF gene amplification in Chinese patients with acral lentiginous melanoma and explore its clinical significance. METHODS A total of 43 patients of ALM were collected between January 1st 2010 and April 30th 2013. We investigated MITF gene amplification in tumor tissues obtained from these patients using quantitative real-time PCR. Clinicopathological information were collected for further analysis. RESULTS MITF gene amplification was detected in 21 of 43 patients （48.8%）. It was not associated with the age （Х^2=0. 193,P=0. 661）, gender （ Х^2= 0. 587,P=0. 443）, stage （ Х^2=4. 837,P=0. 184）, LDH level （Х^2=0. 451,P=0. 502）, ulceration （Х^2=0. 910,P= 0. 340） and tumor tissue origin （ Х^2=1. 406,P= 0. 236）. However, patients with MITF amplification had a significant higher rate of tumor invasion more than 4 mm （72.7% vs 27.3%; Fisher＇s exact test, P=0. 039）. The overall survival of ALM patients with MITF amplification was 42.4 months （95%CI： 29.7-55.1）, which was not significantly different from MITF non-amplification patients （46.3months, 95%CI： 34.5-58.2, Х^2=0. 287,P〈0. 592）. CONCLUSIONS Our findings suggest that MITF gene amplification rate in Chinese acral lentiginous melanoma is high. Patients with MITF amplification had a significant higher rate of tumor invasion more than 4 mm. It seems to predict a poor prognosis.