MUC5B, CA9 and CLDN18 are potential theranostic markers of gallbladder carcinoma

Abstract

Background

Gallbladder cancer (GBC) is an aggressive tumor usually diagnosed at advanced stages and characterized by a poor prognosis. Using public data of normal human tissues, we found that mRNA and protein levels of MUC5B and CA9 genes are highly enriched in gallbladder tissues. In addition, previous evidence showed that CLDN18 protein expression is higher in GBC. In this study we performed an analysis of these cell surface proteins along the histological progression of GBC in order to identify their theranostic potential.

Methods

Expression of MUC5B, CA9 and CLDN18 was examined by immunohistochemistry in a series of 179 chronic cholecystitis (including 16 metaplastic tissues), 15 dysplasias and 217 GBC samples using tissue microarray analysis. A composite staining score was calculated considering staining intensity and percentage of positive cells.

Results

Immunohistochemistry analysis showed a high expression of MUC5B and CA9 among normal epithelium, metaplastic and dysplastic tissues. However, expression of both proteins was observed in about 50% of GBC samples. By contrast, CLDN18 was absent in normal epithelium, but its expression was higher in metaplastic cells. Among GBC cases, approximately half presented high expression of CLDN18. No associations were found between the expression of MUC5B, CA9 and CLDN18 with any clinicopathological features.

Conclusions

CLDN18 is a new metaplasia marker in gallbladder tissues and is conserved in roughly half of GBC cases. MUC5B and CA9 are highly conserved along GBC histological progression. The three markers are potential theranostic markers, in particular CA9 and CLDN18, for which there are already targeted therapies available.

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