Conflicts of interest None declared.
Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer
Article first published online: 2 MAY 2008
© 2008 The Authors. Journal Compilation © 2008 British Association of Dermatologists
British Journal of Dermatology
Volume 159, Issue 1, pages 162–168, July 2008
How to Cite
Ponti, G., Losi, L., Pellacani, G., Wannesson, L., Cesinaro, A.M., Venesio, T., Petti, C. and Seidenari, S. (2008), Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer. British Journal of Dermatology, 159: 162–168. doi: 10.1111/j.1365-2133.2008.08575.x
- Issue published online: 2 MAY 2008
- Article first published online: 2 MAY 2008
- Accepted for publication 11 February 2008
- familial melanoma syndrome;
- hereditary nonpolyposis colorectal cancer;
- malignant melanoma;
- mismatch repair genes;
Background Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed.
Objectives To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC.
Methods Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, β-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM.
Results Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM.
Conclusions Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.