By Jake B. Guinto, PhD, Manager, Oncology Drugs & Biologics
This year's ASCO Annual Meeting held June 1 – 5, 2012, at McCormick Place in Chicago, IL, featured an abstract entitled, "MET and ALK in glioblastoma multiforme (GBM): Comparison of IHC and FISH," which was accepted for both poster presentation and discussion. The research, presented by Dr. Kimary Kulig, Vice President, Clinical & Translational Outcomes Research of the National Comprehensive Cancer Network® (NCCN®) and authored by Dr. Kulig along with several investigators from Duke Cancer Institute, focused on understanding the possible role of ALK (anaplastic lymphoma kinase) and MET (mesenchymal-epithelial transition) in glioblastoma multiforme (GBM).
To gain a better understanding of the role of ALK and MET in GBM, Dr. Kulig and colleagues obtained tumor samples from 56 patients diagnosed with Grade IV malignant GBM from the Duke Brain Tumor tissue bank. Using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques, the investigators visualized ALK and MET protein and DNA expression, respectively. According to their results, among the 56 GBM cases, MET was expressed in 69.9% and ALK in 17.9% of cases through IHC; whereas, by FISH, MET gain or amplification was found in 100% of the GBM cases while ALK was found in 48.2% of the cases. Co-expression of both MET and ALK was 14.3% through IHC and 48.2% by FISH.
Based on the difference between the IHC and FISH expression patterns, the authors suggest that a gain or amplification of gene expression may not always lead to abnormal MET and ALK protein expression. In addition, they suggest that the IHC technique utilized in the study may need to be optimized. Dr. Kulig and colleagues' research contributes to the overall understanding of targetable biomarkers in GBM. Their study supports ALK overexpression observed in glioma cell lines. Furthermore, ALK and MET signaling may have implications for dual-inhibition and potential treatment resistance pathways in GBM. This research may have implications for MET-targeted therapy since it found that MET gain/amplification and protein expression may be higher than previously reported.
This study was partially supported by Pfizer Oncology through an Outcomes Research services agreement. To view the abstract, visit http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=96835