title: Reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system.
abstract: BACKGROUND
  The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson (NSBR) histological grading system for invasive breast cancer (IBC) adopted by the World Health Organization (WHO) has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system.
  
  
  METHODS
  Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index (Ki-67LI) was determined by immunohistochemistry, and its correlations with histological grade and survival were determined.
  
  
  RESULTS
  With respect to interobserver reproducibility, NSBR grading was fairly reproducible (kappa = 0.34); as for the components of NSBR grading, agreement was best for tubule formation (kappa = 0.46), intermediate for nuclear pleomorphism (kappa = 0.42), and poorest for mitotic count (kappa = 0.28). In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading (kappa = 0.30 - 0.69) and nuclear pleomorphism (kappa = 0.28 - 0.69), moderate to substantial for tubule formation (kappa = 0.51 - 0.78), and slight to substantial for mitotic count (kappa = 0.19 - 0.71). There were characteristic Ki-67LI ranges for grades 1, 2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival.
  
  
  CONCLUSIONS
  The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate grading and treatment for IBC. Ki-67, with proven prognostic significance, adds complementary value to the NSBR system.
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Hui-jiao
authors.initials: HJ
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Wei
authors.forename: Hong-ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Zong-guo
authors.initials: ZG
authors.lastname: Pang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D055815:Young Adult