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.
Highlights
Small bowel carcinoma (SBC) is a rare malignancy, in contrast to colorectal carcinoma
Compared to the normal epithelium, MUC1 (p,0.001), MUC5AC (p = 0.019) and MUC16 (p = 0.022) expression was significantly increased in SBC; MUC4 and MUC6 expression showed equal expression; and MUC2 (p,0.001) and MUC3 (p = 0.036) expression was significantly decreased in SBC
[14] In the present study of 60 cases, we found that increased expression of MUC1, MUC5AC and MUC16 in SBCs was related to poor prognostic factors such as deeper invasion, venous invasion, lymph node metastasis, and cases in which only noncurative resection was possible
Summary
Small bowel carcinoma (SBC) is a rare malignancy, in contrast to colorectal carcinoma. Lymph node metastasis [1,2,3], distant metastasis [6], primary tumor status [2,6] and tumor differentiation [1] have been reported as prognostic factors in SBC. Eighteen core human mucins (MUC1–MUC8, MUC12, MUC13, MUC15–17 and MUC19–21) have been identified. The first cloned mucin, MUC1, is an important human tumor antigen, ranking second after WT1 [8]. Aberrant expression of MUC3, MUC4, MUC5AC and MUC6 has been described in pancreatic intraepithelial neoplasia [10,11], and we recently reported that MUC16 is a candidate as a poor prognostic factor in cholangiocarcinoma [12]
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