肺神经内分泌癌c-kit蛋白表达的临床病理意义

目的探讨ckit癌基因蛋白在肺神经内分泌癌中的表达及其临床病理意义。方法采用免疫组化SP法检测90例肺神经内分泌癌患者癌组织中ckit蛋白表达并分析其与各临床病理指标及预后的关系。结果ckit蛋白表达定位于癌细胞胞膜及胞质;ckit表达阳性率分别为类癌21.4%(3/14),不典型类癌90.0%(18/20),大细胞神经内分泌癌38.7%(12/31),小细胞癌76.0%(19/25),差异有统计学意义(P=0.000)。ckit表达癌在Ⅰ期为26.3%(5/19),Ⅱ期62.5%(15/24),Ⅲ期67.4%(29/43),Ⅳ期75.0%(3/4),差异有统计学意义(P=0.014)。ckit在患者性别中的分布为男性64.8%(46/71),女性31.6%(6/19),差异有统计学意义(P=0.017)。ckit表达癌在肿瘤直径大小的分布为<5cm者43.1%(22/51),≥5cm者76.9%(30/39),差异有统计学意义(P=0.002)。ckit表达在淋巴结转移患者为66.1%(47/71),无转移者26.3%(5/19),差异有统计学意义(P=0.003)。ckit阴性表达癌患者的中位生存时间为97个月,ckit阳性癌的患者中位生存时间为16个月,二者比较差异有统计学意义(LogRank=22.85,P=0.000)。ckit蛋白表达与患者肿瘤部位(P=1.000)、年龄(P=0.394)无关。结论ckit蛋白在肺神经内分泌癌的发生、演进过程中起着重要作用,并可作为分子指标监测患者预后。

Clinicopathological significance of expression of c-kit protein in neuroendocrine lung carcinoma

OBJECTIVE: To investigate the expression of c-kit protein in neuroendocrine lung carcinoma and evaluate its clinicopathological significance. METHODS: The expression of c-kit protein in the 90 specimens of neuroendocrine lung carcinoma obtained during operation was detected by immunohistochemistry. The relationship between the expression of c-kit protein and the clinicopathological indices was analyzed statistically. RESULTS: The positive staining of c-kit protein was mainly localized on the membrane and in the cytoplasm of the tumor cells. The positive expression rates of c-kit protein were 21.4% (3/14), 90.0% (18/20), 38.7% (12/31), and 76.0% (19/25) in the carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell lung cancer respectively with significant differences between any 2 histological types (P = 0.000). The c-kit protein expression rate was 26.3% (5/19) in the stage I carcinoma, 62.5% (15/24) in the stage II carcinoma, 67.4% (29/43) in the stage III carcinoma, and 75.0% (3/4) in the stage IV carcinoma with significant differences between any 2 stages (P = 0.014); was 43.1% (22/51) in the tumors less than 5 cm in diameter, and 76.9% (30/39) in the cancers equal to or more than 5 cm in diameter (P = 0.002); 66.1% (47/71) in the tumors with lymphatic metastasis and 26.3% (5/19) in those without lymphatic metastasis (P = 0.003); and 64.8% (46/71) in the males patients and 31.6% (6/19) in the female patients (P = 0.017). Statistical analysis showed that the expression of c-kit protein was not related to age (P = 0.394) and localization (P = 1.000). The median survival in patients with c-kit negative tumors was 97 months, whereas that in those with c-kit positive carcinomas was 16 months (Log rank = 22.85, P = 0.0000). CONCLUSION: c-kit protein expression appears to play an important biological or clinical role in the development and evolution of neuroendocrine lung carcinoma, and may become a useful molecular marker to predict the prognosis of patients. Thus targeted therapies interacting with c-kit-signaling pathway should be taken into account for possible future clinical trials.