Response to Letter to Editor by Cornelissen et al.

To the Editor:

We thank Cornelissen et al.¹ for their interest in our work regarding ALK gene rearrangement in young patients with mesothelioma and its clinical significance.² However, they believe that our conclusion that the presence of the ALK translocation in these patients should be assessed using fluorescence in situ hybridization (FISH) technique was too bold. Their comments are well taken. As they correctly pointed out, our study did not compare different methods of detecting ALK translocation, such as FISH versus immunohistochemistry (IHC)—the two frequently used methods for detecting such translocations in other cancers. ALK translocations have been well studied in lung cancer, with about 5% of patients with NSCLC harboring ALK rearrangements.³ As mentioned by Cornelissen et al.,¹ there are several studies indicating discordance between FISH and IHC in the identification of ALK rearrangement in patients with lung adenocarcinoma, and that the use of IHC may improve detection of ALK rearrangements.^4–6

However, the optimal method to detect ALK translocations is not well-defined for patients with mesothelioma. Because FISH is one of the assays used to select patients with lung cancer for treatment with ALK inhibitors, we chose to use this technique as the initial method to detect ALK rearrangement in our patients.³ However, it is possible that other approaches, such as IHC, may be equivalent to or better than FISH. Thus, we are in agreement with Cornelissen et al.¹ to evaluate the different methods of detecting ALK translocation in patients with mesothelioma so that we can use the most sensitive and specific assay in clinical practice. This is all the more important because patients with mesothelioma harboring such mutations may benefit from ALK inhibitors.⁷