title: Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Shanghai Medical College, and the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, the Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. Electronic address: hqchen1@yahoo.com.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009857:Oncogenes / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm