title: Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma.
abstract: BACKGROUND
  Nuclear grading involves an evaluation of the size and shape of nuclei and the percentage of tumor cells that are in the mitotic phase. To estimate the degree of aggressiveness, this approach has been applied to various types of carcinomas, such as breast carcinoma and pulmonary adenocarcinoma (Nakazato et al.). In the present study, we estimated and evaluated the interobserver variability of nuclear grading in primary pulmonary adenocarcinomas.
  
  
  METHODS
  We selected 122 primary pulmonary adenocarcinomas measuring 2 cm or less in diameter. Eight pathologists independently evaluated the nuclear factors, using the nuclear grading system reported previously by Nakazato et al. The same pathologists also used both the international multidisciplinary classification of pulmonary adenocarcinoma (2011 International Association for the Study of Lung Cancer classification) and Noguchi's classification, and assessed the extent of the lepidic pattern in the largest cut surface of the tumor. Interobserver agreement was evaluated using the κ statistic. The disease-free survival curves of the patients were obtained using the Kaplan-Meier method and analyzed with the log-rank test.
  
  
  RESULTS
  The mean (±SD) κ values for the two histological classifications, the extent of the lepidic pattern, and nuclear grading were 0.46 ± 0.09, 0.48 ± 0.09, 0.45 ± 0.16, and 0.58 ± 0.09, respectively. The cases judged as negative on the basis of nuclear grading showed a significantly better prognosis (5-year disease-free survival rate; 91.8% ± 2.7) than the positive cases did (68.6% ± 3.1).
  
  
  CONCLUSIONS
  : Nuclear grading is practical for prognostic evaluation of pulmonary adenocarcinoma. The interobserver agreement for nuclear grading is significantly higher than for histological classifications and the extent of the lepidic pattern. Nuclear grading is a reliable prognostic indicator for small adenocarcinomas.
authors.affiliation: Department of Anatomic and Diagnostic Pathology, Dokkyo University School of Medicine, Mibu, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Akiko Miyagi
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Minami
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Keisei
authors.initials: K
authors.lastname: Tachibana
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Goya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015588:Observer Variation; D011379:Prognosis; D015996:Survival Rate