EML4-ALK fusion transcripts in immunohistochemically ALK-positive non-small cell lung carcinomas.

EML4-ALK fusion transcripts have been found in a subset of non-small cell lung carcinomas (NSCLCs); however, their protein expression status has not yet been fully elucidated. In this study we investigated ALK protein expression in 302 NSCLCs and 291 gastric carcinomas by means of immunohistochemical analysis. Twelve (4.0%) NSCLCs, but none of the gastric carcinomas, were found to be positive for ALK. The ALK signal was detected in the cytoplasm of cancer cells. Subsequent RNA analysis of 10 RNA-available, immunohistochemically ALK-positive tumors revealed that three tumors had EML4-ALK variant 1, three tumors had variant 2, three tumors had variants 3a and 3b, and one tumor had a novel variant in which exon 14 of EML4 is connected to the nucleotide at position 53 of exon 20 of ALK by a 2-bp insertion. These results suggest that immunohistochemical ALK detection is a useful way to screen NSCLCs for tumors containing ALK fusions.