Protein Expression and Gene Rearrangement of ALK in Non-Small Cell Lung Carcinomas
JH Paik, JY Choe, JH Chung. Seoul National University College of Medicine, Seoul, Korea; Tumor Immunity Medical Research Center at Seoul National University College of Medicine, Seoul, Korea; Seoul National University Bundang Hospital, Seongnam, Korea
Background: A subset of non-small cell lung carcinoma (NSCLC) is associated with anaplastic lymphoma kinase (ALK) gene translocation, mainly forming echinoderm microtubule associated protein like 4 (EML4)-ALK fusion gene. The frequencies of ALK gene translocation have been variably reported depending on detection methods and geographic areas. We investigated the frequencies of (1) ALK protein expression, (2) fusion gene EML4-ALK and (3) the correlation between protein expression and transforming fusion gene EML4-ALK in 470 NSCLC specimens of Korean patients.
Design: From May 2003 to December 2008, 470 consecutive surgically resected cases of NSCLC at Seoul National University Bundang Hospital were enrolled in this study. ALK protein expression was detected by immunohistochemistry and EML4-ALK gene translocation by fluorescent in situ hybridization (FISH) using LSI ALK dual color break-apart rearrangement probe.
Results: ALK protein immunoreactivity was detected in 30 out of 470 NSCLC cases (6.4%), consisting of 28 adenocarcinomas, one squamous cell carcinoma and one atypical carcinoid tumor. On FISH analysis, 14 out of 470 NSCLC cases (3.0%) showed ALK locus rearrangement, all of which showed ALK protein expression by immunohistochemistry. Specifically, ALK gene break-apart was observed in nine adenocarcinoma cases, while another five cases containing four adenocarcinomas and one squamous cell carcinoma showed isolated orange signal.
Conclusions: ALK immunoreactivity in NSCLC was correlated with ALK locus translocation by FISH despite immunohistochemistry and FISH analysis showed a discrepancy in detection rate. These results suggest that ALK immunohistochemistry may be a useful detection method to screen the presence of EML4-ALK fusion transcript. The two methods might be mutually complementary if the mechanism of the discrepancy is well clarified, which would provide more information for new therapeutic options.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 241, Monday Morning