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ROS 1 expression and translocations in non‐small‐cell lung cancer: clinicopathological analysis of 1478 cases
Author(s) -
Warth Arne,
Muley Thomas,
Dienemann Hendrik,
Goeppert Benjamin,
Stenzinger Albrecht,
Schnabel Philipp A,
Schirmacher Peter,
Penzel Roland,
Weichert Wilko
Publication year - 2014
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12379
Subject(s) - kras , immunohistochemistry , lung cancer , cancer research , adenocarcinoma , chromosomal translocation , oncogene , biology , cancer , crizotinib , tyrosine kinase , pathology , oncology , medicine , cell cycle , receptor , gene , genetics , colorectal cancer , malignant pleural effusion
Aims Molecular characterization of non‐small‐cell lung cancer ( NSCLC ) has revealed multiple druggable mutations for targeted therapies. Recently, chromosomal rearrangements involving c‐ros oncogene 1, receptor tyrosine kinase ( ROS 1 ) were identified, and patients seem to benefit from crizotinib treatment. The aim of this study was to identify the clinicopathological characteristics of NSCLC with ROS 1 expression and translocation. Methods and results We screened 1478 NSCLC s with a ROS 1‐specific antibody, and tested positive cases with FISH . All positive cases were analysed for associated clinicopathological characteristics, including survival and molecular tumour composition. Sixty‐eight cases (4.6%) showed ROS 1 immunoreactivity, and ROS 1 translocations were confirmed in nine cases (0.6%). ROS 1 expression was predominantly found in female adenocarcinoma patients, in patients with low T stages, and in association with TTF 1 and napsin expression, and certain histomorphological adenocarcinoma patterns (lepidic, acinar, and solid). ROS 1 translocations occurred in conjunction with other driver mutations ( EGFR , KRAS , and BRAF ). ROS 1 expression was found to be a stage‐independent predictor of favourable survival. Conclusions ROS 1 translocations are rare events in resected NSCLC s from Caucasian patients. Immunohistochemical screening for ROS 1 expression and clinicopathological parameters, including female sex, early tumour stages, adenocarcinomas with TTF 1 and/or napsin expression, and a distinct histomorphological growth pattern, strongly facilitate case enrichment. Molecularly driven multistep concepts might not be optimal for case selection.