Immunohistochemical screening and fluorescence in situ hybridization confirmation of ALK translocation in lung adenocarcinoma and its clinicopathological significance: a single-center large-scale investigation of Chinese patients.

ABSTRACT

Anaplastic lymphoma kinase (ALK) translocation-positive adenocarcinoma of the lung is a newly recognized molecular subgroup. Limited data on the clinicopathological features of this entity in the Chinese population are available. We performed immunohistochemical staining for the ALK protein and fluorescence in situ hybridization detection of the ALK translocation. We enrolled 793 Chinese patients with lung adenocarcinoma and identified 54 ALK translocation-positive patients (6.8%) in the group. Compared with the entire group of patients, ALK translocation-positive patients were younger (P < .01) and more likely to be nonsmokers (P = .017), but presented with a higher percentage of advanced-stage disease (P = .022) and lymph node metastases (P = .006). ALK translocation-positive patients more commonly exhibited poorly differentiated tumor histology and a predominantly solid tumor growth pattern relative to the ALK translocation-negative patients. Morphologically, ALK translocation was associated with extracellular mucus secretion, a mucinous cribriform structure, and signet ring cell (SRC) components. ALK translocation was present in 42.5% and 34.0% of adenocarcinomas with SRC components or wild-type EGFR, respectively. ALK translocation, occurring at a frequency of 6.8% in Chinese patients, defines a unique molecular subgroup of lung tumors. Fluorescence in situ hybridization should be performed in each case of lung adenocarcinoma with SRC components or wild-type EGFR to identify ALK translocation-positive patients.