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 K, Yonezawa Suguru
Department of Palliative Care, Toyota Kosei Hospital, Toyota, Japan.
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
PLoS One. 2014 Apr 10;9(4):e86111. doi: 10.1371/journal.pone.0086111. eCollection 2014.
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.
黏蛋白已被证实与多种癌症患者的生存率相关,但尚未有关于小肠癌(SBC)中黏蛋白的研究。在本研究中,我们调查了60例SBC病例中黏蛋白表达与临床病理因素之间的关系,通过免疫组织化学检测了癌组织和正常组织中MUC1、MUC2、MUC3、MUC4、MUC5AC、MUC6和MUC16的表达谱。与正常上皮相比,SBC病变中MUC1、MUC5AC和MUC16的表达增加,并且这些黏蛋白的表达与临床病理因素相关,具体如下:MUC1[肿瘤位置(p = 0.019)、深度(p = 0.017)和可治愈性(p = 0.007)],MUC5AC[肿瘤位置(p = 0.063)和淋巴结转移(p = 0.059)],以及MUC16[静脉侵犯(p = 0.016)和可治愈性(p = 0.016)]。对58例有生存数据的病例进行分析,发现有五个因素与预后不良相关:低分化或神经内分泌组织学类型(p<0.001)、淋巴结转移(p<0.001)、淋巴管侵犯(p = 0.026)、静脉侵犯(p<0.001)和根治性切除(p<0.001),此外还有MUC1(p = 0.042)、MUC5AC(p = 0.007)和MUC16(p<0.001)的表达。在随后以可治愈性作为协变量的多因素分析中,淋巴结转移、静脉侵犯以及MUC5AC和/或MUC16的表达与预后显著相关。对根治性病例(n = 45)进行多因素分析显示,在调整静脉侵犯的影响后,MUC5AC和/或MUC16表达的SBC具有显著独立的高风险(风险比:5.6,95%置信区间:1.8 - 17)。总之,该研究表明MUC5AC阳性和/或MUC16阳性状态可作为SBC患者预后不良的预测指标。