Παρασκευή 16 Φεβρουαρίου 2018

Detection of ROS1-positive non-small cell lung cancer on cytological specimens using immunocytochemistry

BACKGROUND

Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens. In the current study, the authors explored the accuracy of ROS1 immunocytochemistry (ICC) on non-cell block cytological specimens for the detection of ROS1 rearrangements.

METHODS

ICC using the D4D6 antibody on an automated immunostainer was performed prospectively in the routine diagnostic setting on cytological specimens from 295 patients with NSCLC, including adenocarcinoma (241 patients), NSCLC not otherwise specified (50 patients), and other malignancies (4 patients). Any immunostaining was considered positive.

RESULTS

ICC was positive in all 13 ROS1-rearranged NSCLC cases confirmed by FISH (12 cases) or next-generation sequencing (1 case). Confirmation of 282 ICC-negative cases was available for 208 patients. The sensitivity, specificity, and positive and negative predictive values for ROS1 ICC compared with the final ROS1 status all were 100%.

CONCLUSIONS

ROS1 ICC is an accurate method for the detection of ROS1 rearrangements in NSCLC. Given the high costs and technical challenges of FISH and the rarity of ROS1 rearrangements, ICC is rapid and therefore well suited as a screening method. Cases with equivocal or positive findings on ICC can be confirmed by FISH or molecular tests. Cancer Cytopathol 2018. © 2018 American Cancer Society.



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