Phenotype of Lung Adenocarcinoma with EML-ALK Fusion in the Western Population
SJ Rodig, S Dacic, BY Yeap, JA Barletta, K Law, N Lindeman, AJ Iafrate, LR Chirieac. Brigham & Women's Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; University of Pittsburgh, Pittsburgh, PA
Background: Approximately 3% of lung adenocarcinomas within the Asian population have an interstitial inversion in chromosome 2p resulting in the EML4-ALK fusion gene (ALK+) which is sensitive to ALK inhibitors. The prevalence, epidemiological and morphological characteristics of this abnormality in the Western population is unknown and establishing the appropriate confirmatory diagnostic tests is critical.
Design: We screened tumor specimens from 2 groups of patients with lung adenocarcinoma by immunohistochemical staining (IHC) for ALK protein expression and fluorescent in-situ hybridization analysis (FISH) for the EML4-ALK gene fusion. The first group consisted of 280 unselected cases from 2 institutions (BWH, Boston=155; University of Pittsburgh=125). A second group were lung adenocarcinomas from a selected cohort of patients accrued in a trial conducted at a third institution (MGH, Boston=83).
Results: Within the first group of cases, we identified only 1 tumor (1/280 cases; 0.4%) with an EML4-ALK fusion. Within the second group, we identified 11 tumors (11/83 cases; 13%) with EML4-ALK fusion. Relative to all patients with NSCLC in the United States, we find that patients with ALK+ tumors are more likely to be female (75% vs. 36%; p= .007), younger (median age 52 vs. 66 years; p= .019), and non-smokers (58% vs. 15%; p< .001). In addition, all ALK+ tumors were EGFR wild type (12/12 cases). Although a broad spectrum of histologic patterns were represented among the ALK+ tumors, we found a predominance of signet-ring cell/mucinous histology (4/12 cases).
Conclusions: ALK+ NSCLC is very rare in the Western population. Our results define the features of the molecular subtype of lung adenocarcinomas with EML4-ALK fusion. Suspected cases are best evaluated for the EML4-ALK fusion gene by both IHC and FISH to ensure an accurate diagnosis in triaging for the appropriate targeted therapy.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 240, Tuesday Afternoon