Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas

Yasumasa Yoshioka, Yosuke Togashi, Takaaki Chikugo, Akihiro Kogita, Masataka Taguri, Masato Terashima, Takuro Mizukami, Hidetoshi Hayashi, Kazuko Sakai, Marco A. De Velasco, Shuta Tomida, Yoshihiko Fujita, Tadao Tokoro, Akihiko Ito, Kiyotaka Okuno, Kazuto Nishio

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Abstract

BACKGROUND Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. Cancer 2015;121:4359-68.

Original languageEnglish
Pages (from-to)4359-4368
Number of pages10
JournalCancer
Volume121
Issue number24
DOIs
Publication statusPublished - Dec 15 2015
Externally publishedYes

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Mucinous Adenocarcinoma
Disease-Free Survival
Colorectal Neoplasms
Mutation
Survival

Keywords

  • adenomatous polyposis coli (APC) mutation
  • colorectal mucinous adenocarcinoma
  • histological grading
  • Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation
  • next-generation sequencing
  • SMAD family member 4 (SMAD4) mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yoshioka, Y., Togashi, Y., Chikugo, T., Kogita, A., Taguri, M., Terashima, M., ... Nishio, K. (2015). Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas. Cancer, 121(24), 4359-4368. https://doi.org/10.1002/cncr.29676

Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas. / Yoshioka, Yasumasa; Togashi, Yosuke; Chikugo, Takaaki; Kogita, Akihiro; Taguri, Masataka; Terashima, Masato; Mizukami, Takuro; Hayashi, Hidetoshi; Sakai, Kazuko; De Velasco, Marco A.; Tomida, Shuta; Fujita, Yoshihiko; Tokoro, Tadao; Ito, Akihiko; Okuno, Kiyotaka; Nishio, Kazuto.

In: Cancer, Vol. 121, No. 24, 15.12.2015, p. 4359-4368.

Research output: Contribution to journalArticle

Yoshioka, Y, Togashi, Y, Chikugo, T, Kogita, A, Taguri, M, Terashima, M, Mizukami, T, Hayashi, H, Sakai, K, De Velasco, MA, Tomida, S, Fujita, Y, Tokoro, T, Ito, A, Okuno, K & Nishio, K 2015, 'Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas', Cancer, vol. 121, no. 24, pp. 4359-4368. https://doi.org/10.1002/cncr.29676
Yoshioka Y, Togashi Y, Chikugo T, Kogita A, Taguri M, Terashima M et al. Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas. Cancer. 2015 Dec 15;121(24):4359-4368. https://doi.org/10.1002/cncr.29676
Yoshioka, Yasumasa ; Togashi, Yosuke ; Chikugo, Takaaki ; Kogita, Akihiro ; Taguri, Masataka ; Terashima, Masato ; Mizukami, Takuro ; Hayashi, Hidetoshi ; Sakai, Kazuko ; De Velasco, Marco A. ; Tomida, Shuta ; Fujita, Yoshihiko ; Tokoro, Tadao ; Ito, Akihiko ; Okuno, Kiyotaka ; Nishio, Kazuto. / Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas. In: Cancer. 2015 ; Vol. 121, No. 24. pp. 4359-4368.
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abstract = "BACKGROUND Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS A total of 1373 patients with CRC were analyzed. Forty patients (2.9{\%}) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. Cancer 2015;121:4359-68.",
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T1 - Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas

AU - Yoshioka, Yasumasa

AU - Togashi, Yosuke

AU - Chikugo, Takaaki

AU - Kogita, Akihiro

AU - Taguri, Masataka

AU - Terashima, Masato

AU - Mizukami, Takuro

AU - Hayashi, Hidetoshi

AU - Sakai, Kazuko

AU - De Velasco, Marco A.

AU - Tomida, Shuta

AU - Fujita, Yoshihiko

AU - Tokoro, Tadao

AU - Ito, Akihiko

AU - Okuno, Kiyotaka

AU - Nishio, Kazuto

PY - 2015/12/15

Y1 - 2015/12/15

N2 - BACKGROUND Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. Cancer 2015;121:4359-68.

AB - BACKGROUND Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings. Cancer 2015;121:4359-68.

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KW - histological grading

KW - Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation

KW - next-generation sequencing

KW - SMAD family member 4 (SMAD4) mutation

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