非小细胞肺癌中Ventana ALK免疫组化异质性分析

Interpretation of heterogeneity of Ventana ALK immunohistochemistry in non-small cell lung cancer

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中Ventana间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)免疫组化异质性的分子变异特点和临床病理特征。方法收集2228例NSCLC进行Ventana ALK(D5F3)免疫组化染色,并采用双盲法进行评价。对其中的Ventana ALK异质性病例行FISH和下一代测序(next generation sequencing,NGS)检测。结果Ventana ALK阳性201例(9.0%),异质性10例(0.4%),阴性2017例(90.5%)。Ventana ALK异质性病例包括2例大细胞神经内分泌癌、1例淋巴上皮瘤样癌和7例鳞状细胞癌。Ventana ALK异质性病例中强阳性肿瘤细胞占1%~30%。FISH检测ALK分离信号为0~12%,均为FISH阴性。9例ALK异质性病例成功经NGS检测,均未见ALK基因变异(包括基因融合、拷贝数变异、插入/缺失或单核苷酸变异)。结论Ventana ALK异质性NSCLC应行其他分子病理学检测以进一步确认其ALK基因状态。

Purpose To analyze molecular variability and clinicopathological features of non-small cell lung cancer(NSCLC)with heterogeneity of Ventana anaplastic lymphoma kinase(ALK)immunohistochemistry(IHC).Methods A total of 2228 NSCLC cases were collected for Ventana ALK(D5F3)immunohistochemical staining and evaluated by double-blind method.Fluorescence in situ hybridization(FISH)and next generation sequencing(NGS)were used for Ventana ALK-heterogeneous cases.Results There were 201(9.0%)Ventana ALK-positive cases,10(0.4%)ALK-heterogeneous cases,and 2017(90.5%)ALK-negative cases.Ventana ALK-heterogeneous cases included 2 large cell neuroendocrine carcinomas,1 lymphoid epithelioid carcinoma and 7 squamous cell carcinomas.Strong positive tumor cells accounted for 1%to 30%in Ventana ALK-heterogeneous cases.The ALK FISH break apart signal were 0 to 12%,indicating ALK FISH was negative.Nine ALK-heterogeneous cases were successfully detected by NGS,and no ALK gene variations(including gene fusion,copy number variation,insertion/deletion or single nucleotide variation)were observed.Conclusion Ventana ALK-heterogeneous NSCLC should be further confirmed by other molecular pathological tests.