ORIGINAL ARTICLE

Wnt ligand expression in malignant melanoma: pilot study indicating correlation with histopathological features

K Pham¹, T Milovanovic¹, R J Barr², T Truong¹, R F Holcombe¹

¹ Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92868, USA
² Department of Dermatology, University of California

Correspondence to:
Correspondence to:
Professor R F Holcombe, Division of Hematology/Oncology, UCI Medical Center, Bld 23, Room 244, 101 The City Drive, Orange, CA 92868, USA;
Rholcomb{at}uci.edu

Aims: Secreted Wnt ligands are key proteins regulating cell–cell interactions and cell growth and differentiation. These proteins, along with other components of the Wnt signalling pathway, are involved in the malignant transformation of various human cancers, including malignant melanoma. This study defines the expression of several members of the Wnt ligand family and correlates their expression with histological characteristics.

Methods: The expression of Wnt2, Wnt5a, Wnt5b, Wnt7b, and Wnt10b was defined by in situ, antisense RNA hybridisation of paraffin wax embedded sections of benign naevi and malignant melanoma. Immunoperoxidase based antibody staining was used to define the expression of frizzled (Fz) receptors.

Results: All naevi tested strongly expressed Wnt2, Wnt5a, Wnt7b, and Wnt10b. Melanomas characterised by small, uniform cells expressed each of the Wnts in a pattern similar to that seen for benign naevi. In contrast, melanomas characterised by large, pleomorphic cells expressed Wnt10b but did not express Wnt2 and had low levels of expression of Wnt5a. Expression of Wnt7b was variable in these melanomas. Fz receptor expression was present at a low level in normal epithelium and all naevi and melanomas.

Conclusions: The expression pattern of Wnt ligands in malignant melanoma correlates with histopathological features and may provide a basis for the molecular classification of this disease.

Keywords: Wnt; Frizzled; melanoma; naevi; signal transduction; in situ hybridisation

Abbreviations: APC, adenomatous polyposis coli; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; Fz, Frizzled receptor; LEF1, lymphoid effector factor 1; Mitf, microphthalmia associated transcription factor; TCF, T cell factor

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