title: Alterations of a spectrum of driver genes in female Chinese patients with advanced or metastatic squamous cell carcinoma of the lung.
abstract: OBJECTIVE
  Female patients with squamous cell carcinomas of the lung (SQCLC) in China differ from male patients in that most females are life-long never/light smokers. We hypothesized that the clinical characteristics and mutation profiles of a spectrum of driver genes in Chinese female patients with advanced SQCLC would also differ from those of male patients.
  
  
  METHODS
  We examined the pathological subtype of SQCLC retrospectively by immunohistochemistry (IHC) and screened 38 female and 40 male patients with IIIB/IV-stage SQCLC in China from 2009 to 2012. Mutation analyses of EGFR, PIK3CA, KRAS, and PTEN were performed using PCR-based DNA sequencing. FGFR1 amplification and ALK rearrangements were detected by fluorescent in situ hybridization (FISH). A Cox regression model was used to assess the association between clinical features and genomic mutation status.
  
  
  RESULTS
  There were significantly fewer female patients with a history of smoking than males (5.3% vs. 90%; P<0.001). A younger average age at diagnosis (54.5 vs. 61 years; P=0.032) and a higher percentage of peripheral-type disease (47.4% vs. 25.0%; P=0.040) were observed in females. No difference in ECOG score, tumor size, metastatic status, or overall survival between females and males was seen. PIK3CA mutations were significantly less common in female patients than males (0/38 vs. 6/40; P=0.026). However, no significant difference in the mutational frequencies of EGFR, KRAS, PTEN, ALK, or FGFR1 was observed between females and males.
  
  
  CONCLUSIONS
  Our data demonstrated that female patients with SQCLC are apparently a subtype, with a significantly lower percentage having a smoking history, a younger average age at diagnosis, a higher percentage of peripheral-type disease on radiological presentation, and a lower frequency of PIK3CA mutations. Given the similar survival outcomes between the genders, whether it is a distinct disease entity needs to be studied further in larger populations.
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Qiong
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Wang Yi
authors.initials: WY
authors.lastname: Na
authors.affiliation: Pathology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Bo
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ling
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Mou Hai
authors.initials: MH
authors.lastname: Bo
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Tang Ye
authors.initials: TY
authors.lastname: Min
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Hu Dan
authors.initials: HD
authors.lastname: Na
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Bo
authors.affiliation: Thoracic Oncology Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
authors.forename: Liu Jun
authors.initials: LJ
authors.lastname: Fang
authors.affiliation: Hepatobiliary and Pancreatic Surgery Department, The First Affiliated Hospital Zhejiang University, Hangzhou, China. Electronic address: Tango654321@gmail.com.
authors.forename: Zheng Shu
authors.initials: ZS
authors.lastname: Seng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers
keywords: ALK; EGFR; Non-small cell lung cancer; PIK3CA; Smoking; Squamous cell carcinoma