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Original Research: Lung Cancer |

Comprehensive Analysis of Oncogenic Mutations in Lung Squamous Cell Carcinoma With Minor Glandular ComponentMutations in Lung Squamous Cell Carcinomas

Yunjian Pan, MD; Rui Wang, MD; Ting Ye, MD; Chenguang Li, MD; Haichuan Hu, MD; Yongfu Yu, MS; Yang Zhang, MD; Lei Wang, MD; Xiaoyang Luo, MD; Hang Li, MD; Yuan Li, MD; Lei Shen, MD; Yihua Sun, MD; Haiquan Chen, MD, FCCP
Author and Funding Information

From the Department of Thoracic Surgery (Drs Pan, R. Wang, Ye, C. Li, Hu, Zhang, L. Wang, Luo, H. Li, Sun, and Chen), and the Department of Pathology (Drs Y. Li and Shen), Fudan University Shanghai Cancer Center; and the Department of Oncology (Drs Pan, R. Wang, Ye, C. Li, Hu, Zhang, L. Wang, Luo, H. Li, Y. Li, Shen, Sun, and Chen), Shanghai Medical College, and the Department of Biostatistics (Mr Yu), School of Public Health, Fudan University, Shanghai, China.

Correspondence to: Haiquan Chen, MD, FCCP, Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong’An Rd, Shanghai 200032, China; e-mail: hqchen1@yahoo.com


Drs Pan, R. Wang, Ye, and C. Li contributed to this work equally and should be considered co-first authors. Drs Chen and Sun contributed to this work equally.

Funding/Support: This study was supported by the National Natural Science Foundation of China [Grant 81101761, 81172218] and the Key Construction Program of the National “985” Project Grant [985-YFX0102].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(3):473-479. doi:10.1378/chest.12-2679
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Background:  The mutations in oncogenic genes, such as EGFR, ALK, BRAF, HER2, DDR2, RET, and AKT1, defined subsets of non-small cell lung cancers (NSCLCs) with potential sensitivity to targeted therapies. At present, the mutational spectrum, prevalence, and clinicopathologic characteristics in squamous cell carcinomas with minor (< 10%) glandular component (SQCC-mGCs) are not well established.

Methods:  Three hundred ten surgically resected lung squamous cell carcinoma (SQCC) specimens were collected. The histology of all cases was reevaluated using hematoxylin-eosin and immunohistochemistry staining. EGFR, KRAS, HER2, BRAF, PIK3CA, AKT1, and DDR2 mutations, as well as ALK and RET rearrangements, were examined in 310 SQCCs by directed sequencing.

Results:  Ninety-five SQCC-mGCs (30.6%) and 215 pure SQCCs (69.4%) were identified. Of the 95 SQCC-mGCs, 26 (27.4%; 95% CI, 18.7%-37.4%) were found to harbor known oncogenic mutations, including 10 with EGFR, seven with KRAS, three with PIK3CA, one with BRAF, one with HER2, one each with EGFR/PIK3CA and KRAS/PIK3CA double mutations, and two with EML4-ALK fusions. Ten of 215 pure SQCCs (4.7%; 95% CI, 2.3%-8.4%) harbored mutations, including seven with PIK3CA, and each with AKT1, DDR2, and EGFR. No RET rearrangements were detected in SQCCs. SQCC-mGCs had a significantly higher rate of mutations in known oncogenic genes than that in pure SQCCs (27.4% vs 4.7%, P < .001). All KRAS mutations occurred in SQCC-mGCs.

Conclusions:  Our results demonstrated that oncogenic mutations in EGFR, KRAS, BRAF, HER2, and ALK were extremely rare or absent in patients with pure SQCC, whereas SQCC-mGC had a relatively high frequency of EGFR, ALK, or KRAS mutations. Prospective identification of these known oncogenic mutations in SQCC-mGC before the initiation of treatment is an essential step to identify which patient could benefit from targeted therapies.

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