title: Nuclear grade based on transbronchial cytology is an independent prognostic factor in patients with advanced, unresectable non-small cell lung cancer.
abstract: BACKGROUND
  In patients with resected non-small cell lung cancer (NSCLC), the prognostic value of nuclear grade has been demonstrated. However, among patients with advanced, unresectable NSCLC, the prognostic usefulness of cytological nuclear grade to the authors' knowledge remains unknown. In the current study, the authors used transbronchial cytology to investigate whether nuclear morphometry correlated with clinical outcomes in patients with advanced NSCLC.
  
  
  METHODS
  The authors reviewed patients with advanced, unresectable NSCLC who were diagnosed on transbronchial cytology and were treated at the study institution from 2007 through 2015 (97 patients). Nuclear morphometry (including major diameter) was assessed by an image analysis system and small lymphocytes were used as a reference. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and multivariate analyses were performed using the Cox proportional hazards regression model.
  
  
  RESULTS
  In the multivariate analysis, according to the nuclear major diameter as assessed by an image analysis system, a nuclear major diameter >15 μm was an independent prognostic factor of worse OS (hazard ratio [HR], 1.05; P = .003) and PFS (HR, 1.04; P = 0.011). According to the nuclear major diameter as assessed by small lymphocytes, a major diameter of >5 small lymphocytes was an independent prognostic factor of worse OS (HR, 1.32; P<.001) and PFS (HR, 1.20; P = 0.001). A moderately significant correlation between nuclear diameter measurements by an image analysis system and small lymphocytes was observed (P<.001; correlation coefficient, 0.662).
  
  
  CONCLUSIONS
  Nuclear grade based on nuclear diameter was found to be independently associated with prognosis in patients with advanced, unresectable NSCLC. Cancer Cytopathol 2016;124:630-40. © 2016 American Cancer Society.
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan. qichi@med.kagawa-u.ac.jp.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyai
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Katsuki
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kushida
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Okuda
authors.affiliation: Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kanaji
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Bandoh
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Reiji
authors.initials: R
authors.lastname: Haba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001980:Bronchi / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology*; D003581:Cytodiagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor
keywords: cytology; grade; non-small cell lung cancer; nuclear diameter; prognosis