title: Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.
abstract: OBJECTIVE
  Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th edition's decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.
  
  
  METHODS
  Patients with adenocarcinoma of the appendix diagnosed between 1988 and 2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage, and grade was calculated, and Cox proportional hazards regression analyses were performed.
  
  
  RESULTS
  We analyzed a total of 2469 appendiceal adenocarcinomas, of which 1375 had mucinous histology and 860 had nonmucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female sex, stage IV disease, and well-differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 [95% confidence interval (CI): 1.14-2.34] and 4.94 (95% CI: 3.32-7.35) for mucinous histology, in comparison with 1.44 (95% CI: 0.82-2.52) and 1.90 (95% CI: 0.95-3.80) for nonmucinous histology, respectively.
  
  
  CONCLUSIONS
  The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and these data do not support the combination of these 2 histological grades in the recent AJCC Staging Manual 7th edition.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. moverman@mdanderson.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.forename: Keith
authors.initials: K
authors.lastname: Fournier
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Hu
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: Melissa
authors.initials: M
authors.lastname: Taggart
authors.forename: Richard
authors.initials: R
authors.lastname: Royal
authors.forename: Paul
authors.initials: P
authors.lastname: Mansfield
authors.forename: George J
authors.initials: GJ
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000473:pathology; D000368:Aged; D001063:Appendiceal Neoplasms / Q000473:pathology*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018426:SEER Program; D015996:Survival Rate