title: Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma.
abstract: BACKGROUND
  Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features.
  
  
  METHODS
  Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations.
  
  
  RESULTS
  Compared to CRC without signet-ring cell component, 1-50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02-1.93], and >50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53-8.12) (P trend < 0.0001). Compared to CRC without mucinous component, neither 1-50 % mucinous component (multivariate HR 1.04; 95 % CI 0.81-1.33) nor >50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54-1.23) was significantly associated with CRC-specific mortality (P trend < 0.57).
  
  
  CONCLUSIONS
  Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Mai
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Sun A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Mika
authors.initials: M
authors.lastname: Yasunari
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.|Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins