EML4-ALK Fusion Gene-Positive Lung Cancer: Its Usefulness in Immunohistochemical Screening and Its Histological Variation
Koji Nagata, Michio Shimizu, Shingo Ishiguro. Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; PCL Japan, Suginami-ku, Tokyo, Japan
Background: ALK fusion gene-positive (ALK+) lung cancer was discovered in 2007, and its clinical application of targeted therapy for ALK by crizotinib began in 2012 in Japan. Therefore, in all EGFR/KRAS-negative adenocarcinomas, an examination for ALK rearrangements is recommended. However, ALK-fluorescence in situ hybridization (FISH) testing is time- and cost-consuming, and it is not suitable for a large-scale screening, in contrast to immunohistochemistry (IHC). Regarding the histological types, ALK+ lung cancer has been reported to be associated with a specific histologic type, such as solid, micropapillary, and papillary-predominant patterns and tumor cells with a signet ring or hepatoid cytomorphology.
Design: We prospectively evaluated 259 cases of lung cancer, including primary surgical specimens, metastatic lesions, small biopsy specimens, and cytology cell block specimens, in which all cases were EGFR/KRAS-negative. We investigated the usefulness of ALK+ lung cancer screening by IHC, and evaluated a histologic type of ALK+ lung cancer. The result of IHC was classified into positive, equivocal, and negative. FISH was performed in all cases except for some IHC-negative cases.
Results: Twenty-two cases out of 23 IHC-positive cases were positive for FISH, and 1 out of 3 IHC equivocal cases were positive for FISH (total 8.9%). In the IHC-negative cases, all cases revealed FISH negativity. Of the FISH-positive cases, male-to-female ratio was 5:17, and average age was 56.2 (ranging from 35 to 77 years). As for the histological type, 43% (10/23) showed solid adenocarcinoma; 22% (5/23) acinar adenocarcinoma; 26% (6/23) papillary adenocarcinoma; and 4% (1/23) micropapillary carcinoma. More than half of the cases (12/23) showed intracytoplasmic mucin production including signet-ring appearance.
Conclusions: A good correlation was observed between IHC-positive cases and FISH-positive cases. No specific histologic types were found in ALK+ lung cancer. Our study indicates that immunohistochemical screening is useful and should be performed in all cases of lung cancer since histologic type alone cannot precisely detect ALK+ lung cancers. Further study is needed to evaluate whether or not FISH should be performed in all IHC-positive cases.
Monday, March 4, 2013 1:00 PM
Poster Session II # 282, Monday Afternoon