Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
Hum Pathol. 2010 Oct;41(10):1405-12. doi: 10.1016/j.humpath.2010.02.010. Epub 2010 Jul 1.
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.
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，我们旨在评估 KIT 表达与默克尔细胞癌的结果以及 KIT 基因中激活突变的存在之间的相关性。从 40 名被诊断为默克尔细胞癌的患者中确定了 49 个肿瘤，其中 30 个病例来自 21 名患者用于研究。使用福尔马林固定、石蜡包埋的材料通过免疫组织化学评估 KIT 表达。将病例分为低表达者（0-1+染色强度）和高表达者（2-3+染色强度）。对高 KIT 表达的病例进行 KIT 基因外显子 9、11、13、17 和 18 的直接测序，跨越细胞外、跨膜和酪氨酸激酶结构域。对 21 名患者的 30 个肿瘤进行了 KIT 表达分析。在 67%的患者中观察到高 KIT 表达。在表达高水平 KIT 的肿瘤与低水平 KIT 的肿瘤相比，5 年生存率分别为 0%和 57.8%；然而，这种显著差异没有达到统计学意义（P=0.07）。在分析的 18 个肿瘤中总共发现了 4 个点突变。其中 2 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 2 个突变可能代表新的多态性。我们的工作表明 KIT 表达与默克尔细胞癌患者预后较差之间存在相关性，这提示该受体在肿瘤进展和转移中可能发挥积极作用。然而，我们没有在分析的任何肿瘤中发现 KIT 激活突变。
