Prognostic value of mucin 4 expression in colorectal adenocarcinomas

Authors

  • Chandrakumar Shanmugam MD,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Nirag C. Jhala MD,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Venkat R. Katkoori PhD,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Wen Wan PhD,

    1. Department of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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  • Sreelatha Meleth PhD,

    1. Department of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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  • William E. Grizzle MD, PhD,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
    2. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
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  • Upender Manne PhD

    Corresponding author
    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
    2. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
    • Department of Pathology, University of Alabama at Birmingham K515B1-Kracke Building, 1922, Seventh Avenue South, Birmingham, AL 35294-7331===

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    • Fax: (205) 934-4418


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 = .007) than patients who had with low expression. Patients who had advanced-stage CRCs (stages III and IV) did not demonstrate such a difference (log-rank; P = .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).

CONCLUSIONS:

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. © 2010 American Cancer Society.

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