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

摘要

Objective: The novel fully automated immunohistochemistry(IHC) assay-Ventana anaplastic lymphoma kinase(ALK)-D5F3 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 adenocarcinoma cases 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 clinicopathological 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(χ~2=42.011, P<0.05).ALK(+) adenocarcinoma with lymph node metastasis(10.8%) were significantly higher than that without lymph node metastasis(4.5%)(χ~2=19.809, P<0.05); and ALK(+) in phase Ⅳ(20%) was significantly higher than phase Ⅲ(12.9%), phase Ⅱ(4.2%), phase Ⅰ(4.5%), and phase 0(0)(χ~2=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 mostly seen in younger, clinically higher staging, mucinous and solid predominant adenocarcinoma.Clinical trials in patients of Stage Ⅳ confirmed that ALK-D5F3 Ventana IHC is serviceable in screening ALK-positive candidates for molecular targeted therapy.