title: The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma.
abstract: BACKGROUND
  Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC).
  
  
  METHODS
  All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed.
  
  
  RESULTS
  A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS.
  
  
  CONCLUSIONS
  SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Postlewait
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Malcolm H
authors.initials: MH
authors.lastname: Squires
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Poultsides
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bloomston
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Votanopoulos
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Aslam
authors.initials: A
authors.lastname: Ejaz
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Alexandra W
authors.initials: AW
authors.lastname: Acher
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Worhunsky
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Saunders
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Swords
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Linda X
authors.initials: LX
authors.lastname: Jin
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Winslow
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cardona
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. smaithe@emory.edu.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate