MUC6 down-regulation correlates with gastric carcinoma progression and a poor prognosis: an immunohistochemical study with tissue microarrays

Abstract

Purpose: MUC6 was first discovered by screening a gastric mucosa cDNA library and is expressed in the mucous cells of the neck zone and antral glands of the stomach. The aim of the present study was to clarify whether down-regulation has any clinicopathological or prognostic significance in gastric neoplasia.

Methods: Expression of MUC6, MUC5AC and MUC2 was examined using tissue microarrays for immunohistochemistry in gastric carcinomas (n = 225), adenomas (n = 40), and normal mucosa (n = 89) and compared with clinicopathological parameters and survival data.

Results: MUC6 expression was lower in gastric carcinomas than in adenomas or normal mucosa (P < 0.05) and inversely correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC staging (P < 0.05). Positive links with expression of MUC2 and MUC5AC were noted (P < 0.05). MUC6 expression was lower in diffuse-type than intestinal-type lesions (P < 0.05). Kaplan-Meier analysis indicated that cumulative survival of patients with no MUC6 expression was significantly lower than with weak, moderate or strong expression in all and even advanced gastric carcinoma (P < 0.05). Multivariate analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to concordantly affect the relationship between MUC6 expression and prognosis.

Conclusions: Down-regulation of MUC6 may contribute to malignant transformation of gastric epithelial cells and underlie the molecular bases of growth, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behaviors and prognosis of gastric carcinoma.

Fig. 1

HE staining and immunohistochemistry of gastric samples. HE staining of TMA of gastric carcinoma (a). Immunoreactivities to MUC2, MUC5AC and MUC6 distributed to the cytoplasm. Strong expression of MUC6 was shown in gastric gland (b, d), adenoma (c) and carcinoma (e–g). There was strong MUC6 expression in gastric mucosa, but not in gastric signet cell carcinoma (d). Gastric carcinoma displayed strong expression of MUC2 (h) and MUC5AC (i)

Fig. 2

Correlation between status of MUC6 and prognosis of the gastric carcinoma patients. Kaplan–Meier curves for cumulative survival rates of patients with all (a) and even advanced (b) gastric carcinomas according to MUC6 expression