TY - JOUR
T1 - Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma
AU - Inamura, Kentaro
AU - Yamauchi, Mai
AU - Nishihara, Reiko
AU - Kim, Sun A.
AU - Mima, Kosuke
AU - Sukawa, Yasutaka
AU - Li, Tingting
AU - Yasunari, Mika
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Meyerhardt, Jeffrey A.
AU - Fuchs, Charles S.
AU - Harris, Curtis C.
AU - Qian, Zhi Rong
AU - Ogino, Shuji
N1 - Publisher Copyright:
© 2014, Society of Surgical Oncology.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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) (Ptrend < 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 (Ptrend < 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.
AB - 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) (Ptrend < 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 (Ptrend < 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.
UR - http://www.scopus.com/inward/record.url?scp=84925504973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925504973&partnerID=8YFLogxK
U2 - 10.1245/s10434-014-4159-7
DO - 10.1245/s10434-014-4159-7
M3 - Article
C2 - 25326395
AN - SCOPUS:84925504973
VL - 22
SP - 1226
EP - 1235
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
IS - 4
ER -