Article Text

Download PDFPDF
Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker
  1. Johanne Lade-Keller1,
  2. Rikke Riber-Hansen1,
  3. Per Guldberg2,
  4. Henrik Schmidt3,
  5. Stephen Jacques Hamilton-Dutoit1,
  6. Torben Steiniche1
  1. 1Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark
  2. 2Danish Cancer Society Research Center, Copenhagen, Denmark
  3. 3Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
  1. Correspondence to Johanne Lade Keller, Institute of Pathology, Aarhus University Hospital, Noerrebrogade 44, Aarhus C DK-8000, Denmark; johanneromer{at}


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.

  • Melanoma
  • Immunohistochemistry
  • Cancer Research
  • Skin Tumours
  • Oncogenes

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.