Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer.
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.
Department of Palliative Care, Toyota Kosei Hospital, Toyota, Japan.
Hiroaki
H
Shibahara
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Michiyo
M
Higashi
Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Chihaya
C
Koriyama
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Seiya
S
Yokoyama
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Iwao
I
Kitazono
Department of Surgery, Toyota Kosei Hospital, Toyota, Japan.
Yasuhiro
Y
Kurumiya
Department of Pathology, Toyota Kosei Hospital, Toyota, Japan.
Michihiko
M
Narita
Department of Surgery, Chutoen General Medical Center, Kakegawa, Japan.
Shingo
S
Kuze
Department of Surgery, Chutoen General Medical Center, Kakegawa, Japan.
Takanori
T
Kyokane
Department of Surgery, Chita City Hospital, Chita, Japan.
Saburo
S
Mita
Department of Surgery, Anjo Kosei Hospital, Anjo, Japan.
Toshiyuki
T
Arai
Department of Surgery, Toyohashi Municipal Hospital, Toyohashi, Japan.
Takehito
T
Kato
Department of Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
Norihiro
N
Yuasa
Department of Surgery, Kasugai Municipal Hospital, Kasugai, Japan.
Ryuzo
R
Yamaguchi
Department of Surgery, Handa City Hospital, Handa, Japan.
Hitoshi
H
Kubota
Department of Surgery, Handa City Hospital, Handa, Japan.
Hideaki
H
Suzuki
Department of Diagnostic Pathology, University Hospital Hamamatsu University School of Medicine, Hamamatsu, Japan.
Satoshi
S
Baba
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, United Kingdom.
Karine
K
Rousseau
Departments of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Surinder K
SK
Batra
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Suguru
S
Yonezawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D018394:CA-125 Antigen / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000401:mortality; D007421:Intestine, Small / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; C524678:MUC5AC protein, human; D008565:Membrane Proteins; D055271:Mucin 5AC; D018396:Mucin-1