title: Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis.
abstract: OBJECTIVE
  To define the prognostic value of different histological subtypes of colorectal cancer.
  
  
  BACKGROUND
  Most colorectal cancers are classical adenocarcinomas (AC). Less frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). In contrast to established prognostic factors such as TNM and grading, the histological subtype has no therapeutical consequences so far, although it may reflect different biological behavior.
  
  
  METHODS
  Between 1982 and 2012, a total of 3479 consecutive patients underwent surgery for primary colorectal cancer (AC, MAC, or SC). Clinical, histopathological, and survival data were analyzed.
  
  
  RESULTS
  Of all 3479 patients, histological subtype was AC in 3074 cases (88%), MAC in 375 cases (11%), and SC in 30 cases (0.9%). MAC (51%, P < 0.001) and SC (50%, P = 0.029) occurred more frequently in right-sided tumors than AC (28%). Compared with AC, tumor stages and histological grading were higher in MAC and SC (P < 0.001 for each). Rates of angioinvasion were lower in MAC than in AC (5% vs 9%, P = 0.011). Rates of lymphatic invasion were higher in SC than in AC (67% vs 25%, P < 0.001). Five-year cause-specific survival was 67 ± 1% for AC, 61 ± 3% for MAC, and 21 ± 8% for SC (P < 0.001 for difference between the groups). In multivariable analysis, survival did not differ significantly between AC and MAC after correction for tumor stage. However, SC remained an independent prognostic factor associated with worse survival (hazard ratio = 2.5, 95% confidence interval = 1.6-3.8, P < 0.001).
  
  
  CONCLUSIONS
  MAC and SC are histological subtypes of colorectal cancer with different characteristics than classical AC. Both are diagnosed in more advanced tumor stages, but the dismal prognosis of SC seems to be caused by its intrinsic tumor biology.
authors.affiliation: *Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany †Institute of Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany ‡Institute of Pathology, Technische Universität München, Munich, Germany §Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, OR ¶Department of Surgery, Kantonsspital Baden, Baden, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nitsche
authors.forename: Anina
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Christoph
authors.initials: C
authors.lastname: Späth
authors.forename: Tara
authors.initials: T
authors.lastname: Müller
authors.forename: Matthias
authors.initials: M
authors.lastname: Maak
authors.forename: Tibor
authors.initials: T
authors.lastname: Schuster
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Käser
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Janssen
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenberg
authors.forename: Franz G
authors.initials: FG
authors.lastname: Bader
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000473:pathology* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate