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Oncotarget. 2015 Sep 8;6(26):22028-37.

Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.

Author information

1
Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, SE 22381 Lund, Sweden.
2
Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, SE 22185 Lund, Sweden.
3
Department of Pathology, Regional Laboratories Region Skåne, SE 22185 Lund, Sweden.
4
Create Health Strategic Center for Translational Cancer Research, Lund University, Medicon Village, SE 22381 Lund, Sweden.
5
Department of Thoracic Surgery, Lund University, Skåne University Hospital, SE 22185 Lund, Sweden.
6
Department of Oncology, Skåne University Hospital, SE 22185 Lund, Sweden.

Abstract

Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.

KEYWORDS:

ALK; LCNEC; gene fusion; large cell lung cancer; mutation

PMID:
26124082
PMCID:
PMC4673143
DOI:
10.18632/oncotarget.4314
[Indexed for MEDLINE]
Free PMC Article

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