MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas

Abstract

Background: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.

Aims: To investigate the prognostic significance of MUC4 expression in IDC.

Methods: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.

Results: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.

Conclusions: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

Figure 1

Immunohistochemical staining of (A, B) MUC4, (C) ErbB2, (D) p27, and (E) MUC1 in invasive ductal carcinoma of the pancreas. MUC4 was expressed in the carcinoma tissue (A, left), but not in the normal pancreas tissue (A, right) (original magnification, ×40). MUC4 expression was seen in the cytoplasm and/or membrane of the carcinoma cells (B, original magnification, ×160). ErbB2 was expressed in the membrane and/or cytoplasm of the carcinoma cells (C, original magnification, ×160). p27 expression was seen in the nuclei of the carcinoma cells (D, original magnification, ×160). MUC1 was expressed in the membrane and/or cytoplasm of the carcinoma cells (E, original magnification, ×160).

Figure 2

Correlation between MUC4 expression and cumulative survival rate in 135 patients with invasive ductal carcinoma, as determined by the Kaplan–Meier method. The survival of patients with high MUC4 expression was worse than those with low MUC4 expression (p  =  0.0043). The open circles represent those patients who were alive at the last follow up.

Figure 3

Combined evaluation of MUC4 and p27 expression. Patients with both high MUC4 and p27 expression had the worst outcome. In contrast, patients with both low MUC4 and p27 expression had the best outcome. A significant difference for survival was found between the two groups (p < 0.0001). The open circles represent those patients who were alive at the last follow up.