Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status
Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status
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DOI：
10.1016/j.humpath.2010.02.010
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发表时间：
2010-10-01
期刊：
影响因子：
3.3
通讯作者：
Siegal, Gene P.
中科院分区：
文献类型：
--
作者：
Andea, Aleodor A.;Patel, Raj;Siegal, Gene P.
默克尔细胞癌是最具侵袭性的原发性皮肤恶性肿瘤之一。由于一些默克尔细胞癌表达受体酪氨酸激酶KIT，我们的目的是评估KIT表达与默克尔细胞癌预后和KIT基因激活突变的相关性。共从40例诊断为默克尔细胞癌的患者中鉴定出49例肿瘤，其中21例患者中的30例被用于研究。免疫组织化学检测KIT在福尔马林固定石蜡包埋材料上的表达。病例分为低表达者（0-1+染色强度）和高表达者（2-3+染色强度）。对于KIT高表达的病例，对KIT基因跨越细胞外、近膜和酪氨酸激酶结构域的外显子9、11、13、17和18进行直接测序。对21例患者的30个肿瘤进行KIT表达分析。67%的患者高表达KIT。表达高水平KIT和低水平KIT的肿瘤的5年生存率分别为0%和57.8%；然而，这种显著性差异没有达到统计学意义（P = .07）。在分析的18个肿瘤中共鉴定出4个点突变。其中两个是涉及外显子17和18的沉默突变，2个涉及内含子16-17。鉴定出的两个突变可能代表新的多态性。我们的研究表明KIT表达与Merkel细胞癌患者预后不良之间存在相关性，这提高了该受体在肿瘤进展和转移中发挥积极作用的可能性。然而，我们没有在分析的任何肿瘤中发现KIT激活突变。(C) 2010爱思唯尔公司版权所有。
Merkel cell carcinoma is one of the most aggressive primary cutaneous malignancies. Because some Merkel cell carcinomas express the receptor tyrosine kinase KIT, we aimed to evaluate the correlation of KIT expression with the outcome and the presence of activating mutations in the KIT gene in Merkel cell carcinoma. A total of 49 tumors from 40 patients with a diagnosis of Merkel cell carcinoma were identified, of which 30 cases from 21 patients were used in the study. KIT expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded material. Cases were divided into low expressors (0-1+ staining intensity) and high expressors (2-3+ staining intensity). Direct sequencing of exons 9, 11, 13, 17, and 18 of the KIT gene spanning the extracellular, juxtamembrane, and tyrosine kinase domains was performed for cases with high KIT expression. Thirty tumors from 21 patients were analyzed for KIT expression. High KIT expression was seen in 67% of the patients. Five-year survival rates in tumors expressing high versus low levels of KIT were 0% versus 57.8%, respectively; however, this dramatic difference did not reach statistical significance (P = .07). A total of 4 point mutations were identified in 18 tumors analyzed. Two of these were silent mutations involving exons 17 and 18, and 2 involved intron 16-17. Two of the identified mutations may represent novel polymorphisms. Our work suggests a correlation between KIT expression and a worse prognosis in Merkel cell carcinoma patients, raising the possibility of an active role of this receptor in tumor progression and metastasis. However, we did not identify KIT activating mutations in any of the tumors analyzed. (C) 2010 Elsevier Inc. All rights reserved.