TY - JOUR T1 - Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker JF - Journal of Clinical Pathology JO - J Clin Pathol SP - 520 LP - 528 DO - 10.1136/jclinpath-2013-202127 VL - 67 IS - 6 AU - Johanne Lade-Keller AU - Rikke Riber-Hansen AU - Per Guldberg AU - Henrik Schmidt AU - Stephen Jacques Hamilton-Dutoit AU - Torben Steiniche Y1 - 2014/06/01 UR - http://jcp.bmj.com/content/67/6/520.abstract N2 - Aims To perform immunohistochemical (IHC) analysis of molecular drivers related to the development and maintenance of melanoma and to assess their value as diagnostic and prognostic melanoma biomarkers in routine clinical practice. Methods Tissue microarrays constructed from a cohort of primary melanomas (n=355), benign naevi (n=37) and melanoma metastases (n=14) were evaluated for IHC expression of c-KIT, BRAFV600E, MITF, p16, p53 and PTEN, as well as for pERK, a surrogate marker for mitogen-activated protein kinase pathway activation. The results were correlated with clinicopathological parameters and clinical outcome. Results Absent p16 expression and reduced MITF expression were both associated with the adverse prognostic markers ulceration (p=0.009 and p<0.0001, respectively), advanced tumour stage (p<0.0001 and p=0.001, respectively) and higher Breslow thickness (both p<0.0001), as well as with an adverse overall relapse-free survival (p<0.0001 and p=0.003, respectively). Absence of p16 expression predicted overall relapse-free (p=0.02) and distant metastasis-free (p=0.04) survival, independently of Breslow thickness, ulceration and tumour stage. Conclusions IHC determined p16 expression is an independent prognostic biomarker of potential value in routine melanoma diagnostic practice. ER -