Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma

Kentaro Inamura, Mai Yamauchi, Reiko Nishihara, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Tingting Li, Mika Yasunari, Xuehong Zhang, Kana Wu, Jeffrey A. Meyerhardt, Charles S. Fuchs, Curtis C. Harris, Zhi Rong Qian, Shuji Ogino

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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<inf>trend</inf> < 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<inf>trend</inf> < 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.

Original languageEnglish
Pages (from-to)1226-1235
Number of pages10
JournalAnnals of Surgical Oncology
Volume22
Issue number4
DOIs
Publication statusPublished - 2015
Externally publishedYes

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Cellular Structures
Colorectal Neoplasms
Mortality
Confidence Intervals
Microsatellite Instability
CpG Islands
Molecular Epidemiology
Health
Rectal Neoplasms
Proportional Hazards Models
Colonic Neoplasms
Methylation
Neoplasms
Nurses
Databases
Pathology
Phenotype
Mutation
Survival

ASJC Scopus subject areas

  • Surgery
  • Oncology

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Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma. / Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Harris, Curtis C.; Qian, Zhi Rong; Ogino, Shuji.

In: Annals of Surgical Oncology, Vol. 22, No. 4, 2015, p. 1226-1235.

Research output: Contribution to journalArticle

Inamura, K, Yamauchi, M, Nishihara, R, Kim, SA, Mima, K, Sukawa, Y, Li, T, Yasunari, M, Zhang, X, Wu, K, Meyerhardt, JA, Fuchs, CS, Harris, CC, Qian, ZR & Ogino, S 2015, 'Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma', Annals of Surgical Oncology, vol. 22, no. 4, pp. 1226-1235. https://doi.org/10.1245/s10434-014-4159-7
Inamura, Kentaro ; Yamauchi, Mai ; Nishihara, Reiko ; Kim, Sun A. ; Mima, Kosuke ; Sukawa, Yasutaka ; Li, Tingting ; Yasunari, Mika ; Zhang, Xuehong ; Wu, Kana ; Meyerhardt, Jeffrey A. ; Fuchs, Charles S. ; Harris, Curtis C. ; Qian, Zhi Rong ; Ogino, Shuji. / Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma. In: Annals of Surgical Oncology. 2015 ; Vol. 22, No. 4. pp. 1226-1235.
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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) (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.",
author = "Kentaro Inamura and Mai Yamauchi and Reiko Nishihara and Kim, {Sun A.} and Kosuke Mima and Yasutaka Sukawa and Tingting Li and Mika Yasunari and Xuehong Zhang and Kana Wu and Meyerhardt, {Jeffrey A.} and Fuchs, {Charles S.} and Harris, {Curtis C.} and Qian, {Zhi Rong} and Shuji Ogino",
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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

PY - 2015

Y1 - 2015

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.

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