title: Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?
abstract: OBJECTIVE
  To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.
  
  
  METHODS
  Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.
  
  
  RESULTS
  cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.
  
  
  CONCLUSIONS
  Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
authors.affiliation: Luca Reggiani Bonetti, Federica Domati, Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, 41124 Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Reggiani Bonetti
authors.affiliation: Luca Reggiani Bonetti, Federica Domati, Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, 41124 Modena, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lionti
authors.affiliation: Luca Reggiani Bonetti, Federica Domati, Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, 41124 Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Domati
authors.affiliation: Luca Reggiani Bonetti, Federica Domati, Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, 41124 Modena, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002454:Cell Differentiation; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: Acellular mucin pools; Downstaging; Dworak; Mucinous; Rectal carcinoma