非小细胞肺癌中ALK蛋白表达与临床病理相关

Association of ALK protein expression with clinical pathology in non-small cell lung cancer

目的探讨间变性淋巴瘤激酶(ALK)与非小细胞肺癌(NSCLC)的病理特征之间的关系。方法用VENTANA ALK(D5F3)免疫组织化学法(IHC)检测125例NSCLC患者手术切除的石蜡标本中ALK蛋白的表达情况,用荧光原位杂交(FISH)检测ALK蛋白表达阳性病例EML4-ALK融合基因表达情况,分析ALK蛋白的表达与NSCLC临床病理特征及预后之间的关系。结果 125例患者中,ALK蛋白阳性表达15例(12.0%),主要定位于细胞质内,少数位于细胞膜上;ALK蛋白在有吸烟史患者中的阳性表达率显著低于无吸烟史者,在腺癌中阳性表达率显著高于非腺癌,在高-中分化癌中阳性表达率显著低于低分化癌(P<0.05);Kaplan-Meier分析显示ALK阳性的患者预后较阴性好(P<0.05)。15例ALK蛋白阳性病例经FISH验证,10例为FISH阳性。结论 ALK蛋白的表达与NSCLC患者是否有吸烟史、临床病理类型以及肿瘤分化程度有紧密联系。IHC可以作为可靠的ALK筛查手段,提高ALK的检出率。FISH检测对确诊ALK蛋白阳性肺癌具有重要意义。

Objective To investigate the relationship between anaplastic lymphoma kinase (ALK) and the pathological features of non-small cell lung cance (NSCLC). Methods The expression of ALK protein in paraffin-embedded specimens of 125 NSCLC patients was detected by VENTANA ALK (D5F3) immunohistochemical method (IHC). ALK protein expression was detected by fluorescence in situ hybridization (FISH). The expression of EML4-ALK fusion gene was analyzed to identify the relationship between the expression of ALK protein and the clinicopathological features and prognosis of NSCLC. Results The expression of ALK protein was positive in 15 patients (12.0%) in 125 patients. The positive expression of ALK protein was mainly in the cytoplasm and a few on the cell membrane. The positive rate of ALK protein in patients with smoking history was significantly lower than those without smoking history. The positive rate in cancer was significantly higher than that in non-adenocarcinoma, and the positive rate in high-to-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma ( P <0.05). Kaplan-Meier analysis showed that ALK-positive patients had better prognosis than negative ones ( P <0.05). Fifteen ALK protein-positive cases were verified by FISH and 10 cases were FISH positive. Conclusions The expression of ALK protein is closely related to the history of smoking, clinical pathology and tumor differentiation in NSCLC patients. IHC can be used as a reliable ALK screening method to increase the ALK detection rate. FISH detection is of great significance for the diagnosis of ALK protein-positive lung cancer.