Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer

Hiroaki Shibahara, Michiyo Higashi, Chihaya Koriyama, Seiya Yokoyama, Iwao Kitazono, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Takanori Kyokane, Saburo Mita, Toshiyuki Arai, Takehito Kato, Norihiro Yuasa, Ryuzo Yamaguchi, Hitoshi Kubota, Hideaki Suzuki, Satoshi Baba, Karine Rousseau, Surinder Kumar Batra, Suguru Yonezawa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001), lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p<0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8-17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

Original languageEnglish (US)
Article numbere86111
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 10 2014

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Intestinal Neoplasms
mucins
Mucins
carcinoma
Carcinoma
neoplasms
metastasis
lymph nodes
Lymph Nodes
Tumors
Hazards
Neoplasm Metastasis
multivariate analysis
prognosis
Neoplasms
Multivariate Analysis
Survival
resection
lesions (animal)
immunohistochemistry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Shibahara, H., Higashi, M., Koriyama, C., Yokoyama, S., Kitazono, I., Kurumiya, Y., ... Yonezawa, S. (2014). Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer. PloS one, 9(4), [e86111]. https://doi.org/10.1371/journal.pone.0086111

Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer. / Shibahara, Hiroaki; Higashi, Michiyo; Koriyama, Chihaya; Yokoyama, Seiya; Kitazono, Iwao; Kurumiya, Yasuhiro; Narita, Michihiko; Kuze, Shingo; Kyokane, Takanori; Mita, Saburo; Arai, Toshiyuki; Kato, Takehito; Yuasa, Norihiro; Yamaguchi, Ryuzo; Kubota, Hitoshi; Suzuki, Hideaki; Baba, Satoshi; Rousseau, Karine; Batra, Surinder Kumar; Yonezawa, Suguru.

In: PloS one, Vol. 9, No. 4, e86111, 10.04.2014.

Research output: Contribution to journalArticle

Shibahara, H, Higashi, M, Koriyama, C, Yokoyama, S, Kitazono, I, Kurumiya, Y, Narita, M, Kuze, S, Kyokane, T, Mita, S, Arai, T, Kato, T, Yuasa, N, Yamaguchi, R, Kubota, H, Suzuki, H, Baba, S, Rousseau, K, Batra, SK & Yonezawa, S 2014, 'Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer', PloS one, vol. 9, no. 4, e86111. https://doi.org/10.1371/journal.pone.0086111
Shibahara H, Higashi M, Koriyama C, Yokoyama S, Kitazono I, Kurumiya Y et al. Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer. PloS one. 2014 Apr 10;9(4). e86111. https://doi.org/10.1371/journal.pone.0086111
Shibahara, Hiroaki ; Higashi, Michiyo ; Koriyama, Chihaya ; Yokoyama, Seiya ; Kitazono, Iwao ; Kurumiya, Yasuhiro ; Narita, Michihiko ; Kuze, Shingo ; Kyokane, Takanori ; Mita, Saburo ; Arai, Toshiyuki ; Kato, Takehito ; Yuasa, Norihiro ; Yamaguchi, Ryuzo ; Kubota, Hitoshi ; Suzuki, Hideaki ; Baba, Satoshi ; Rousseau, Karine ; Batra, Surinder Kumar ; Yonezawa, Suguru. / Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer. In: PloS one. 2014 ; Vol. 9, No. 4.
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AU - Higashi, Michiyo

AU - Koriyama, Chihaya

AU - Yokoyama, Seiya

AU - Kitazono, Iwao

AU - Kurumiya, Yasuhiro

AU - Narita, Michihiko

AU - Kuze, Shingo

AU - Kyokane, Takanori

AU - Mita, Saburo

AU - Arai, Toshiyuki

AU - Kato, Takehito

AU - Yuasa, Norihiro

AU - Yamaguchi, Ryuzo

AU - Kubota, Hitoshi

AU - Suzuki, Hideaki

AU - Baba, Satoshi

AU - Rousseau, Karine

AU - Batra, Surinder Kumar

AU - Yonezawa, Suguru

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N2 - Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001), lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p<0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8-17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

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