ALK Status in Esophageal Adenocarcinoma and Squamous Carcinoma Studied by DNA Microarray, FISH and Immunohistochemistry
Zhongren Zhou, Santhoshi Bandla, Jiqing Ye, Liqiong Li, Tony Godfrey, Nancy Wang. University of Rochester Medical Center, Rochester, NY
Background: The anaplastic lymphoma kinase (ALK) gene encodes a tyrosine kinase receptor that belongs to the insulin receptor superfamily. The 3'-tyrosine kinase domain is fused to a variety of partners such as NPM-ALK or EML4-ALK leading to express fusion proteins that play oncogenic roles in a variety of malignancies. Using mass spectroscopy alone, TPM4-ALK fusion protein was detected in esophageal squamous cell carcinoma (SCC). To verify the possible role of ALK in SCC and esophageal adenocarcinoma (EAC), we use different approaches to study ALK gene arrangement, amplification or expression.
Design: Genomic DNA from 116 EAC (95 M and 21 F) fresh tissue was analyzed for copy number aberrations using Affymetrix SNP 6.0 arrays. Tissue microarrays constructed at the University of Rochester between 1997 and 2005 included squamous mucosa (SE), EAC and SCC. ALK amplification and rearrangement were detected by FISH and ALK expression was tested by immunohistochemistry (IHC).
Results: By genomic analysis, ALK amplification was found in 7% (8/116) EAC frozen tissue cases by SNP analysis which was confirmed by FISH test in TMA cases (7%; 5/74). However, no ALK expression was identified either in EAC (0/112) or in SCC (0/33) by IHC. No gene rearrangement of ALK was detected in either EAC (0/74) or SCC (0/33) by FISH. No difference of overall survival time was observed between amplified and non-amplified groups in EAC patients.
Conclusions: ALK amplification was present in 7% of EAC cases, but ALK rearrangement and expression was not present. No ALK amplification, rearrangement and expression were detected in SCC. ALK amplification is not associated with EAC patients' overall survival.
Monday, March 4, 2013 1:00 PM
Poster Session II # 118, Monday Afternoon