Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer

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.

A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

“…Sections were incubated with a primary antibody (DF3 diluted 1∶50, 37°C, 32 min; Ccp58 diluted 1∶200, 37°C, 24 min; 8G7 diluted 1∶3000, 37 °C, 32 min; CLH2 diluted 1∶100, 37°C, 24 min; CLH5 diluted 1∶100, 37°C, 24 min; OC125 diluted 1: 100, 37°C, 24 min; anti-human MUC17 diluted 1: 100) in phosphate-buffered saline (PBS) pH 7.4 with 1% bovine serum albumin, and stained on a Benchmark XT automated slide stainer using a diaminobenzidine detection kit (ultraView DAB, Ventana Medical Systems). For MUC3 staining, sections were treated at 100°C for 10 min in 0.01 M citrate buffer at pH 6.0, and then reduced with 0.01 M dithiothreitol in 0.1 M Tris/HCl buffer (pH 8.0) for 30 min at room temperature and alkylated with 0.025 M iodoacetamide in 0.1 M Tris/HCl buffer (pH 8.0) for 30 min [13] , [17] , [27] . They were incubated with mMUC3-1 at 4°C for 16 h and stained by avidin-biotin complex method.…”

“…Carcinoma cells are considered to be stained positively when at least one of the components was positive. A tumor was considered positive if more than 5% of carcinoma cells were stained, based on our previous use of 5% as the cutoff for mucin expression [17] , [28] – [33] .…”

“…Yonezawa et al showed that MUC1 and/or MUC4 expression is related to a poorer prognosis for various human cancers, whereas MUC2 expression is related to a better prognosis [10] , [12] . Aberrant expression of MUC3, MUC4, MUC5AC and MUC6 is found in pancreatic intraepithelial neoplasia [13] , [14] , and MUC16 and MUC17 are expressed in pancreatobiliary and small intestinal cancers [15] – [17] and have high prognostic value [15] , [17] – [19] . Mucin expression also occurs in appendiceal carcinoma [20] – [26] , however, there is no study for the relationship between mucin expression and survival of over 100 surgically-treated patients with appendiceal carcinoma.…”

Significance of MUC1 expression in biopsy specimens of submucosal invasive gastric carcinoma: The association with lymph node metastasis

“…ESD guidelines were previously based on hematoxylin and eosin staining; however, numerous studies have reported that the expression of cell adhesion molecules, cell surface molecules, membrane-associated mucin phenotypes and collagen phenotypes are associated with lymph node metastasis and prognosis of carcinomas in multiple organs (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Mucin 1, cell surface associated (MUC1) is a transmembrane member of the mucin family and has been reported to be associated with metastatic progression (16).…”

Mucus-penetrating polymersomes as a potential lung drug delivery system: preparation, in vitro characterization, and biodistribution tests

“…4,5 The study of mucin expression patterns and its regulation becomes a potential strategy in finding cancer biomarkers. [4][5][6][7][8][9] Figure 1 -Tumors use mucins for invasion, metastasis and protection. a.Tumors use the antiadhesive effect of mucins to detach from the tumor mass and surrounding stroma and invade.…”