间变淋巴瘤激酶两种检测法的结果不同

The findings of a recent study indicate that routine testing with both fluorescent¹ in situ hybridization (FISH) and immunohistochemistry (IHC) may enhance the detection of ALK-positive non-small cell lung cancer (NSCLC). Accurate determination of ALK-positive tumors is necessary to identify patients with advanced NSCLC who are most likely to benefit from targeted therapy with an ALK inhibitor. The discovery of ALK rearrangement in about 1% to 7% of NSCLCs led to the development of ALK inhibitors, such as crizotinib, which have significantly improved treatment response among people with ALK-positive NSCLC. FISH with break-apart probes is currently the only approved test for the detection of ALK positivity in NSCLC, but this technique may not be available or feasible（可行的） in all institutions. IHC, which is more affordable² and accessible than FISH, has been found to be reliable as a screening tool, but interpretation³ of its results have not been standardized⁴. Researchers continue to explore the optimal⁵ testing process for identifying ALK-positive NSCLCs.

 

Parallel testing with both FISH and IHC on 3,234 NSCLCs led to the identification of 150 tumors that were ALK positive by either test. The results of FISH and IHC were discordant⁶（不和谐的） in 80 of these tumors. As such, the use of FISH or IHC alone would have missed approximately 25% of ALK-positive cases. The findings of the study are published in the March issue of the International Association for the Study of Lung Cancer's journal, the Journal of Thoracic Oncology (JTO).

 

Most discordant results were FISH-positive/IHC-negative (36 cases); FISH-negative/IHC-positive results were found in 19 cases, and FISH-noncontributive/IHC-positive results were found in 15 cases. Preliminary data from 44 evaluable patients showed that treatment with an ALK inhibitor was associated with a high response rate, with response noted⁷ among patients who had tumors with discordant results (either FISH-positive/IHC-negative or FISH-negative/IHC-positive).

 

"Data on crizotinib response in patients who have been diagnosed differently by FISH and IHC are still preliminary（初步的）. Thus, until large-scale studies in patients under therapy with crizotinib determine which testing is the most relevant to predict responses to ALK inhibition, our data support the need to routinely perform both analyses because of the difficulty in detecting the chimeric⁸ ALK protein in NSCLC and the presence of false-negative cases for each method," says lead author Florian Cabillic, PharMD, PhD, Université de Rennes, Rennes, France.

 

The study also demonstrated that systematic⁹ testing of NSCLC by both FISH and IHC is feasible in routine practice. In addition, the findings indicate that performing FISH routinely on all NSCLC specimens¹⁰ may require an automated¹¹ process at various stages of the analysis.

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