The Landscape of Actionable Molecular Alterations in Immunomarker-Defined Large-Cell Carcinoma of the Lung.

Autor:	Chan AW; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Chau SL; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Tong JH; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Chow C; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Kwan JSH; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Chung LY; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Lung RW; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Tong CY; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Tin EK; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Law PP; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Law WT; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China., Ng CSH; Division of Cardiothoracic Surgery, Department of Surgery, the Chinese University of Hong Kong, Hong Kong, China., Wan IYP; Division of Cardiothoracic Surgery, Department of Surgery, the Chinese University of Hong Kong, Hong Kong, China., Mok TSK; Department of Clinical Oncology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China., To KF; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China. Electronic address: kfto@cuhk.edu.hk.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2019 Jul; Vol. 14 (7), pp. 1213-1222. Date of Electronic Publication: 2019 Apr 09.
DOI:	10.1016/j.jtho.2019.03.021
Abstrakt:	Introduction: Patients with pulmonary large-cell carcinoma (LCC) have poor prognosis and limited treatment options. The identification of clinically actionable molecular alterations helps to guide personalized cancer treatment decisions. Patients and Methods: A consecutive cohort of 789 resected NSCLC cases were reviewed. Fifty-nine NSCLC cases lacking morphologic differentiation, accounting for 7.5% of all resected NSCLCs, were identified and further characterized by immunohistochemistry according to the 2015 WHO lung tumor classification. Molecular alterations were investigated by multiple technologies including target capture sequencing, immunohistochemistry, and fluorescence in situ hybridizations. Results: Of 59 NSCLC cases lacking morphologic differentiation, 20 (33.9%) were reclassified as adenocarcinoma (LCC-AD), 14 (23.7%) as squamous cell carcinoma (LCC-SqCC), and 25 (42.4%) as LCC-Null. Approximately 92% of LCC-Null, 95% of LCC-AD, and 86% of LCC-SqCC harbored clinically relevant alterations. Alterations characteristic of adenocarcinoma (EGFR, KRAS, ALK receptor tyrosine kinase [ALK], ROS1, and serine/threonine kinase 11 [STK11]) were detected in the LCC-AD subgroup but not in LCC-SqCC, whereas squamous-lineage alterations (phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha [PIK3CA], SRY-box 2 [SOX2], fibroblast growth factor receptor 1 [FGFR1], and AKT1) were detected in the LCC-SqCC subgroup but not in the LCC-AD group. Although some LCC-Null tumors displayed a genetic profile similar to either adenocarcinoma or squamous-cell carcinoma, more than half of the LCC-Null group were completely devoid of recognizable lineage-specific genetic profiles. High programmed death ligand 1 expression and high frequency of cell cycle regulatory gene alterations were found in the LCC-Null group offering alternative options of targeted therapy. Conclusions: This comprehensive molecular study provided further insight into the genetic architecture of LCC. The presence of clinically actionable alterations in a majority of the tumors allowed personalized treatment to emerge. (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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