Assay aids ALK fusion detection in lung adenonocarcinoma

Sep 6 2013

By Joanna Lyford, Senior medwireNews Reporter

A fully automated immunochemistry (IHC) assay is highly sensitive and specific for detecting anaplastic lymphoma kinase (ALK) fusion in primary lung adenocarcinomas, Chinese researchers report.

The new assay could prove valuable for the rapid identification of patients who are candidates for ALK-targeted treatment, say Jianming Ying (Chinese Academy of Medical Sciences, Beijing, China) and fellow investigators.

ALK gene rearrangement is seen in 2–7% of non-small-cell lung cancers (NSCLCs), and an ALK inhibitor, crizotinib, has recently shown promise in these patients. Thus, “efficient determination of ALK status in NSCLC patients is critical for directing patient care,” explain Ying and co-authors in the Annals of Oncology.

Current methods for detecting ALK fusion are fluorescence in situ hybridization (FISH), real-time reverse transcription–polymerase chain reaction (RT–PCR), and IHC, with FISH being considered the gold standard in clinical trials.

In this study, Ying’s group report their evaluation of a new, fully automated IHC assay (Ventana IHC, Ventana Medical Systems, Tucson, Arizona, USA) in 196 primary lung adenocarcinomas, 63 (32%) of which were considered ALK-positive based on FISH.

The new IHC assay identified ALK protein in 65 (33%) tumors, the authors reveal. These were the same 63 tumors that were classified ALK-positive by FISH plus another two that were ALK-negative by FISH but positive by RT-PCR.

Thus, the IHC assay had a sensitivity of 100% and specificity of 98%.

Other assays were less accurate than Ventana IHC: RT-PCR had a sensitivity of 98% and a specificity of 95%, while an alternative, semiquantitative IHC assay had a sensitivity of 76% and a specificity of 98%.

The investigators conclude that the new assay is a highly sensitive and specific method for detecting ALK rearrangement in primary lung adenocarcinoma.

“Our study demonstrated that some ALK IHC-positive but FISH-negative lung cancers did harbor the translocation events as confirmed by RT–PCR,” they remark.

“Thus, this subgroup of patients should also benefit from ALK inhibitory therapy. Further clinical trials are required to address the predictive value of ALK IHC in these patients.”

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