MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma

Abstract

Background: Peptide sequence homology between the gene product of human MUC4 and rat sialomucin complex (SMC) has recently been reported. Each contains a mucin subunit with antiadhesive activity linked to the plasma membrane by means of a transmembrane subunit with two epidermal growth factor (EGF)-like domains that act as ligand for ErbB2. This study investigates MUC4 and ErbB2 receptor expression in major and minor salivary gland mucoepidermoid carcinoma and correlates patterns of expression with clinical outcomes.

Methods: MUC4 antigens and ErbB2 receptor expression are localized by immunohistochemical studies that use archival formalin-fixed and paraffin-embedded tissue. Clinical outcomes are determined by retrospective chart review of all patients (n = 28) with available archived pathologic specimens at the University of Miami-affiliated hospitals treated between 1994 and 2000.

Results: Median survival time was 24 months (range, 2-60 months) among the nine patients who died, whereas median follow-up time in the remaining 19 patients is 33.4 months (range, 4.7-73 months). A trend toward a reduction in MUC4 antigen expression in high-grade tumors (55% expression) compared with low-grade (91% expression) and intermediate-grade (100% expression) tumors is identified (chi square, p =.0975). Patients with tumors expressing MUC4 antigens are at reduced risk of death (hazard ratio [HR], 0.20; p =.0531). Adjustment for pathologic grade, T stage, and age results in a much higher risk of death for patients whose tumors do not express MUC4 antigens, although this does not meet statistical significance (HR, 26.6; p =.1). Analysis of recurrence adjusting for T stage reveals that patients whose tumors do not express MUC4 antigens are at increased risk of recurrence compared with patients whose tumor expresses MUC4 antigens (HR, 6.37; p =.03). ErbB2 receptor staining is noted in seven of 28 patients, with five of these seven showing 2+ and 3+ membrane-staining patterns. Adjustment for pathologic grade and age suggests that patients whose tumors express high levels of ErbB2 (2+, 3+) are at increased risk of death compared with patients with low or no expression of ErbB2 (HR, 2.29; p =.32). MUC4 antigen positivity is seen in two of the five cases with 2+ and 3+ staining for ErbB2. CONCLUSIONS.: These findings suggest MUC4 antigen positivity is associated with reduced risk of death and reduced risk of recurrence and may identify a subset of patients with more favorable prognosis. Although limited by small sample size, analysis reveals ErbB2 overexpression is not consistently associated with MUC4 antigen positivity and might be associated with increased risk of death.