Detection of ALK translocation in non-small cell lung carcinoma （NSCLC） and its clinicopathological significance using the Ventana immunohistochemical staining method： a single-center largescale investigation of 1,504 Chinese Han patients

Objective： The novel fully automated immunohistochemistry （IHC） assay-Ventana anaplastic lymphoma kinase （ALK）-DSF3 for screening ALK rearrangements has been approved by China＇s Food and Drug Administration in 2013, our previous study disclosed a highly specificity and sensitivity nearly 100%, and its efficacy needs to be evaluated in a large cohort of primary lung adenocarcinoma patients, and to compare clinicopathological features with ALK （＋） and ALK （-） lung adenocarcinoma.Methods： A total of 1,504 consecutive surgical lung adenocareinoma eases of Chinese Han population were collected and re-diagnosed according to the 2011 multidisciplinary classification of lung adenocarcinoma. Fully automated Ventana ALK-D5F3 IHC staining with a binary scoring was adopted to evaluate staining and correlated with dinieopathologieal characters, including age, sex, differentiation degree, histological subtype, lymph node metastasis, and clinical staging. ALK （＋） patients were followed-up, and targeted therapy of ALKinhibitors was adopted and observed in patients with stage IV according to the NCCN guideline.Results： ALK positive adenocarcinomas were identified in 6.6% of the surgically resected 1,504 NSCLCs, and significantly younger than the negative group （P〈0.05）.Mucinous adenocarcinoma （28.2%） was determined to be predominant in ALK （＋） cases, followed by the solid type （11.7%）, specific type （6.8%）, papillary type （5.6%）, acinar type （5.5%）, and lepidic type （3.1%）, and the differences were statistically significant （χ2=42.01 1, P〈0.05）. ALK （＋） adenocarcinoma with lymph node metastasis （10.8%） were significantly higher than that without lymph node metastasis （4.5%） （g2=19.809, P〈0.05）; and ALK （＋） in phase Ⅳ （20%） was significantly higher than phaseⅢ （12.9%）, phase Ⅱ （4.2%）, phase Ⅰ （4.5%）, and phase 0 （0） （g2=36.068, P〈0.05）. Multivariate logistic regression disclosed that patient age, AJCC staging, and histological mucinous subtype were correlated with ALK positive staining （OR=0.959, 1.578, 5.036, respectively）. Sixty eight patients had followed-up results, five patients out of which primarily diagnosed or progressed into Stage IV benefited well from targeted therapy with Crizotinib.Conclusions： The ALK fusion protein was seen in 6.6% Chinese NSCLC patients, and mosdy seen in younger, clinically higher staging, mueinous and solid predominant adenoearcinoma. Clinical trials in patients of Stage Ⅳ eonfirmed that ALK-DSF3 Ventana IHC is serviceable in screening AL