title: Comprehensive pathological analyses in lung squamous cell carcinoma: single cell invasion, nuclear diameter, and tumor budding are independent prognostic factors for worse outcomes.
abstract: BACKGROUND
  For lung squamous cell carcinomas, there are no pathological findings that have been universally accepted as prognostic factors, with the exception of pathological stage. Tumor budding and nuclear grade have been recognized as a poor prognostic factor in other carcinomas. In this study, we investigated whether pathological findings could determine prognosis in lung squamous cell carcinomas.
  
  
  METHODS
  All available tumor slides from patients with surgically resected, solitary lung squamous cell carcinomas (1999-2009) were reviewed (n = 485; stage I/II/III, 281/136/68). Tumors were evaluated for differentiation, subtypes (keratinizing, nonkeratinizing, basaloid pattern, papillary growth, and clear cell feature), tumor nest size (tumor budding and single cell invasion), and nuclear grade (nuclear diameter and mitosis). Overall survival (OS) was estimated using the Kaplan-Meier method (stratified by pathological stage), and group differences were investigated using the stratified log-rank test and the Cox proportional hazards model.
  
  
  RESULTS
  OS was significantly decreased in patients with versus without single cell invasion (p = 0.002 for the entire tumor and p = 0.001 for tumor edge), with large versus small nuclei (p = 0.011), and with high versus low grade tumor budding (p < 0.001 for maximum and p = 0.007 for total). In multivariate analyses, single cell invasion (hazard ratio [HR], 1.47-1.49), nuclear diameter (HR, 1.09-1.33), and tumor budding (HR, 1.04) were independent prognostic factors of OS. However, histologic subtyping including keratinizing, nonkeratinizing, basaloid, and clear cell subtypes did not show prognostic significance.
  
  
  CONCLUSIONS
  Pathological factors can help stratify prognosis in patients with lung squamous cell carcinomas.
authors.affiliation: *Thoracic Service, Department of Surgery; †Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; ‡Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa; §Department of Thoracic Surgery, The University of Tokyo, Tokyo, Japan; ‖Department of Epidemiology and Biostatistics; and ¶Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nitadori
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: David J
authors.initials: DJ
authors.lastname: Finley
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000601:surgery; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005355:Fibrosis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate