Prognostic value of mucin 4 expression in colorectal adenocarcinomas

Abstract

BACKGROUND: Mucin 4 (MUC4) is aberrantly expressed in colorectal adenocarcinomas (CRCs) but its prognostic value is unknown. METHODS: Archival tissue specimens collected from 132 CRC patients who underwent surgical resection without presurgery or postsurgery therapy were evaluated for expression of MUC4 by using a mouse monoclonal antibody and horseradish peroxidase. MUC4 expression levels were correlated with clinicopathologic features and patient survival. Survival was estimated by both univariate Kaplan-Meier and multivariate Cox regression methods. RESULTS: In both normal colonic epithelium and CRCs, MUC4 staining was localized primarily in the cytoplasm. The optimal immunostaining cutoff value (!75% positive cells and an immunostaining score !2.0), which was derived by using the bootstrap method, was used to categorize CRCs into groups of high expression (33 of 132 patients; 25%) or low expression (99 of 132 patients; 75%). Patients who had early stage tumors (stages I and II) with high MUC4 expression had a shorter disease-specific survival (log-rank; P ¼ .007) than patients who had with low expression. Patients who had advanced-stage CRCs (stages III and IV) did not demonstrate such a difference (logrank; P ¼ .108). Multivariate regression models that were generated separately for patients with early stage and advanced-stage CRC confirmed that increased expression of MUC4 was an independent indicator of a poor prognosis only for patients who had early stage CRCs (hazard ratio, 3.77; 95% confidence interval, 1.46-9.73). CONCLU-SIONS: The current results indicated that increased MUC4 expression is a predictor of poor survival in CRC, specifically for patients who have early stage tumors. Cancer 2010;116;3577-86.

MiR-150-5p Suppresses Colorectal Cancer Cell Migration and Invasion through Targeting MUC4

“…MUC4 is frequently deregulated in a wide variety of cancers (Carraway et al, 2002), and its over-expression has been associated with a poor prognosis and survival in various carcinomas, including colon carcinomas (Shanmugam et al, 2010). Furthermore, increasing evidence also indicate MUC4 is critical for the progression of other malignancies (Ponnusamy et al, 2008;Rachagani et al, 2012;Mukhopadhyay et al, 2013).…”

“…Expression analysis of MUC4 in CRC demonstrated CRC patients with increased MUC4 expression had short survival compared to low expressors (Shanmugam et al, 2010). However, there is still little known about the molecular mechanisms that regulate MUC4 expression in CRC.…”

Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma

“…In addition, prostate cancer has exhibited downregulation of MUC4 expression in prostate carcinomas as compared with that in the normal/benign prostate regions. In contrast to the aforementioned studies, high MUC4 expression correlates with a short disease-free interval and a poor survival rate of small-sized lung adenocarcinomas, cholangiocarcinomas, epithelial ovarian carcinomas, pancreatic cancers and colorectal adenocarcinoma (12)(13)(14)(15)(16)25,26). MUC4 overexpression in gastric cancer tissues compared with normal adjacent tissues has been previously reported (27).…”

Immunohistochemistry of colorectal carcinoma: current practice and evolving applications

“…To the extent that increased MUC2 expression is associated with mucinous differentiation and MSI, increased MUC2 expression may be predictive of resistance to 5-fluorouracil, irinotecan, and platinum-based (oxaliplatin) therapies because these mucinous tumors often demonstrate overexpression of thymidylate synthase and glutathione S-transferase [38]. Although similar diagnostic limitations also apply to MUC1 and MUC4, the expression of these mucins has been found to be associated with aggressive behavior in a number of studies [35,37,[39][40][41][42][43].…”