title: Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.
abstract: BACKGROUND
  Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC).
  
  
  METHODS
  We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.
  
  
  RESULTS
  Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87).
  
  
  CONCLUSIONS
  Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. nhiraoka@ncc.go.jp
authors.forename: N
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Ino
authors.forename: S
authors.initials: S
authors.lastname: Sekine
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Kosuge
authors.forename: J
authors.initials: J
authors.lastname: Zavada
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011184:Postoperative Period; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases