¹The Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway

Correspondence: Dr LA Akslen, Children's Hospital, Harvard Medical School, Vascular Biology Program, Karp Family Research Labs 12.125, 300 Longwood Avenue, Boston, MA 02115-5737, USA. E-mail: lars.akslen@childrens.harvard.edu or lars.akslen@gades.uib.no

Received 31 January 2005; Revised 28 July 2005; Accepted 23 August 2005; Published online 27 September 2005.

Abstract

The ID1 protein, an inhibitor of basic helix–loop–helix transcription factors, has been involved in multiple cellular processes including cell cycle regulation, apoptosis, and angiogenesis. To evaluate the importance of ID1 in malignant melanoma, tumour cell expression was examined by immunohistochemistry in 119 cases of nodular melanoma using tissue microarray technique, and related to multiple tumour markers including proliferation, p16 expression, angiogenesis and patient survival. Strong ID1 expression was significantly associated with increased tumour thickness, and significantly reduced survival. Also, increased ID1 was associated with loss of thrombospondin-1 (TSP-1) expression, a known inhibitor of angiogenesis, and increased intensity of ephrin-A1 and its receptor EPHA2. Presence of BRAF mutations was related to strong ID1 expression, but there was no relationship with p16 protein expression. Further, no significant correlation was found between ID1 and microvessel density. In conclusion, our study supports a significant role of the ID1 protein in melanoma progression and patient prognosis. The absence of correlation with p16 protein expression and angiogenesis suggests that other regulatory pathways and mechanisms might be influenced by ID1 in melanomas. An inverse relation between ID1 and TSP-1 expression support an important role of ID1 in the regulation of this complex multitarget protein.