Immunohistochemical screening of ALK lung cancer with biopsy specimens of advanced lung cancer.

Abstract

10532 Background: The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of lung cancers. Low expression of EML4-ALK fusion protein complicates detection by conventional immunohistochemistry. We recently developed intercalated antibody-enhanced polymer (iAEP) immunohistochemistry, which sensitively and specifically detects ALK fusion proteins including EML4-ALK. Here, we aimed to identify and characterize ALK-positive individuals among patients with advanced lung cancer. Methods: We immunohistochemically screened for ALK fusion proteins using biopsy specimens from 492 non-selected patients with advanced lung cancer. The expression of ALK was examined by iAEP and medical records were reviewed. Results: Of the 492 patients, 331 were male and 160 were female. Stages were IIIA (n = 126), IIIB (n = 117), IV (n = 212) and recurrence (n = 36). Histology revealed adenocarcinoma (n = 253; BAC, n = 5), squamous carcinoma (n = 71), large cell carcinoma (n = 36), LCNEC (n = 13), NSCLC (n = 46) and SCLC (n = 72). Of the 492 tumors screened, 10 (2%) were positively stained for ALK and all ALK-positive tumors were adenocarcinoma. The characteristics of the patients with ALK-positive lung cancer were as follows, male:female (3:7), median age: 53 (26-75) years, stage IIIA (n = 3), IIIB (n = 5) and IV (n = 2). Eight patients were light smokers or had never smoked and two were heavy smokers. Patients with ALK-positive lung cancer were significantly younger (p < 0.05), and more likely to be female (70% vs 47%, p < 0.05) than those with ALK-negative lung adenocarcinoma. Among the ALK-positive patients, nine received platinum-based chemotherapy and five (71%) of seven evaluable patients were responders. None of the five patients who received EGFR TKIs were responders. Conclusions: The frequency of ALK-positive lung cancer among patients with advanced lung cancer is similar at the early stage of lung cancer as reported and EGFR TKIs are ineffective whereas platinum doublets might be favorable for these patients. No significant financial relationships to disclose.