1. ¹Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
2. ²Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia
3. ³Department of Medicine, St Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
4. ⁴Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
5. ⁵Melbourne Pathology, Collingwood, Victoria, Australia
6. ⁶Dorevitch Pathology, Heidelberg, Victoria, Australia
7. ⁷Gribbles Pathology, Clayton, Victoria, Australia

Correspondence: Associate Professor Grant A. McArthur, Division of Clinical Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia. E-mail: grant.mcarthur@petermac.org

Received 9 April 2006; Revised 25 July 2006; Accepted 21 August 2006; Published online 7 December 2006.

Abstract

The BRAF^T1799A mutation encodes BRAF^V600E that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAF^T1799A mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAF^T1799A mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAF^T1799A mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAF^T1799A mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); 50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAF^T1799A mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAF^T1799A mutation is associated with a lower rate of tumor proliferation.