Wnt5a Overexpression in Thick Primary Oral Mucosal Melanomas:

Implications for its Role in Tumor Progression

Abstract

Wnt genes encode a large family of secreted cysteine-rich signaling molecules involved in cell growth, differentiation and tumorigenesis. Wnt5a, a non-transforming member of the Wnt family behaves as a putative oncogene in many cancers including melanomas. The aim of our study was to determine Wnt5a expression in primary oral mucosal melanomas (OMM) and correlate it with tumor thickness. Archival tissues from 18 OMM cases were subjected to immunohistochemical detection of Wnt5a by the streptavidin-biotin method. These were categorized into tumors of <4 mm (thin and intermediate thickness lesions) and >4 mm (thick lesions) thickness. Most OMM cases (17/18; 94.4%) stained positive for Wnt5a, though heterogeneously. Seven thick (7/11; 64%) and one intermediate thickness (1/7, 14%) OMM demonstrated strongly positive Wnt5a staining (P<0.05). The only Wnt5a-negative case was a thick OMM without local recurrence after treatment. Strong Wnt5a expression at tumor advancing sites suggests a role in local tumor spread. Identification of pleomorphic epithelioid and spindle cells as melanoma cell populations with the most pronounced Wnt5a staining suggests that Wnt5a overexpression influences cellular phenotype. These results taken together suggest that Wnt5a is up-regulated in OMM and may play a role in tumor progression.