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Ann Surg Oncol. 2015 Apr;22(4):1226-1235. doi: 10.1245/s10434-014-4159-7. Epub 2014 Oct 18.

Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
2
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD.
3
Department of Nutrition, Harvard School of Public Health, Boston, MA.
4
Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China.
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
6
Department of Epidemiology, Harvard School of Public Health, Boston, MA.
7
Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
#
Contributed equally

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.

PMID:
25326395
PMCID:
PMC4346446
DOI:
10.1245/s10434-014-4159-7
[Indexed for MEDLINE]
Free PMC Article

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