Clinico-pathologic features of lung cancer with EML4-ALK translocation.

Abstract

10598 Background: A small subset of human lung cancer harbors the fusion of the gene for echinoderm microtubule-associated protein-like 4 (EML4) and the gene for anaplastic lymphoma kinase (ALK), resulting from a small inversion within chromosome 2p. A phase I dose escalation trial for ALK tyrosine kinase inhibitor showed promising activity against these tumors. We examined our cohort of patients for EML4-ALK translocation and tried to concentrate this rare type of lung cancer according to the clinico-pathologic background of the patients. Methods: Methods We studied 345 patients with lung cancer who underwent pulmonary resection in our hospital (adenocarcinoma 314, large cell carcinoma 5, small cell carcinoma 1, squamous cell carcinoma 21, adenosquamous cell carcinoma 4) after obtaining appropriate informed consent from the patients. EML4-ALK translocation was detected by RT-PCR and direct sequencing. Results: We found 10 EML4-ALK translocations (3%). Seven were variant 1, two variant 2 and one variant 1. All were adenocarcinoma. Eight patients were female and 7 were never-smokers. None of the tumors harbored either of EGFR, KRAS, HER2 or TP53 mutation. The incidence of ALK fusion was 10 of 97 (10%) without any of four mutations. Median age of patients with ALK fusion was 56 that was significantly younger than that of entire cohort (63) or those with EGFR mutation (64) or KRAS mutation (65). Histopathologically, most of the tumors with ALK fusion were solid-acinar type with cribriform pattern. Conclusions: Lung caners with ALK fusion tended to occur in younger female patients with acinar type adencoarcinoma devoid of EGFR, KRAS, HER2 or TP53 mutations. Although this type of lung cancer is rare, we have to establish efficient screening method because genotype-based therapy would be possible in the near future. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer