Kit expression in small cell carcinomas of the lung:: Effects of chemotherapy
Kit expression in small cell carcinomas of the lung:: Effects of chemotherapy
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DOI：
10.1097/01.mp.0000089780.30006.de
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发表时间：
2003-10-01
期刊：
影响因子：
7.5
通讯作者：
Crinò, L
中科院分区：
文献类型：
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作者：
Rossi, G;Cavazza, A;Crinò, L
相当数量的小细胞肺癌表现出原癌基因c-kit产物的过度表达，这是一种被称为Kit或CD117的酪氨酸激酶。这种分子途径似乎在某种程度上促进了小细胞肺癌的肿瘤生长。目前其选择性抑制剂的药理学有效性，以及在治疗CD117阳性肿瘤(如晚期胃肠道间质瘤)方面的良好临床结果，引起了肿瘤学家的极大兴趣，他们希望也对其他CD117阳性肿瘤采用这种治疗策略。我们评估了一系列27例小细胞肺癌，比较了初治肿瘤(一线化疗前)和化疗后复发后同一肿瘤的CD117表达。所有患者均接受相似的化疗方案(顺铂/卡铂+依托泊苷)。确诊时，27例中有21例(78%)CD117呈强免疫反应。在这21例原阳性肿瘤中，10例(48%)复发后仍有CD117高表达，其余11例为阴性。未发现CD117阴性的小细胞癌化疗后呈免疫反应。CD117的表达与总存活率、化疗耐药的发生或临床化疗反应无统计学相关性。我们还检测了46例手术切除的非小细胞肺癌(8例鳞癌，10例腺癌，5例多形性癌，10例典型类癌和3例不典型类癌，10例大细胞神经内分泌癌)中CD117的表达。除小细胞癌外，CD117在10例大细胞神经内分泌癌中有6例呈高表达，其他组织类型均未见表达。我们推测，在高比例的小细胞肺癌中，化疗后CD117表达的缺失表明，在该肿瘤中，Kit不太可能代表结构性突变的产物，而在胃肠道间质瘤中则显示出这一点。考虑到这一发现，肿瘤学家可以重新测试复发小细胞肺癌的CD117表达，以确定参加正在进行的Kit抑制剂临床试验的最佳候选者。实际上，CD117可能有助于区分肺高级别神经内分泌肿瘤和其他组织类型，但病理学家应该意识到，在相当数量的病例中，经治疗的小细胞肺癌可能不染色。
A significant number of small cell lung carcinomas shows overexpression of the proto-oncogene c-kit product, a tyrosine kinase known as Kit or CD117. This molecular pathway seems somewhat implicated in promoting the neoplastic growth of small cell lung carcinoma. The current pharmacological availability of its selective inhibitor, together with the promising clinical results in the management of CD117-posidve neoplasms such as advanced gastrointestinal stromal tumors, aroused great interest among oncologists in also adopting this therapeutic strategy in other CD117-positive tumors. We evaluated a series of 27 small cell lung carcinomas, comparing the expression of CD 117 of the primary naive tumor (before first-line chemotherapy) with the expression of the same neoplasm after postchemotherapy relapse. All the patients underwent similar chemotherapeutic regimens (cisplatin/carboplatin plus etoposide). At diagnosis, 21 of 27 cases (78%) showed strong immunoreactivity for CD117. Among these 21 originally positive tumors, CD 117 remained overexpressed in 10 after relapse (48%), whereas the other 11 cases became negative. No originally CD117-negative small cell carcinomas displayed immunoreactivity after chemotherapy. CD117 expression was not statistically correlated with overall survival, occurrence of chemoresistance, or clinical response to chemotherapy. We also evaluated CD117 expression in a series of 46 surgically resected non-small cell lung carcinomas (8 squamous cell carcinomas, 10 adenocarcinomas, 5 pleomorphic carcinomas, 10 typical and 3 atypical carcinoids, and 10 large cell neuroendocrine carcinomas). Apart from small cell carcinomas, CD117 overexpression was observed in 6 of 10 large cell neuroendocrine carcinomas, whereas all the other histotypes resulted unstained. We speculate that loss of CD117 expression after chemotherapy in a high proportion of SCLC indicates that in this tumor, Kit unlikely represents the product of a constitutive mutation, as instead shown in gastrointestinal stromal tumors. Keeping this finding in mind, oncologists could re-test CD117 expression in relapsing small cell lung carcinomas in order to establish the best candidates for enrollment in ongoing clinical trials with Kit inhibitors. Practically speaking, CD 117 may be helpful in discriminating between pulmonary high-grade neuroendocrine tumors and other histotypes, but pathologists should be aware that treated small cell lung carcinomas may remain unstained in a not insignificant number of cases.