Original article
Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker Johanne Lade-Keller,1 Rikke Riber-Hansen,1 Per Guldberg,2 Henrik Schmidt,3 Stephen Jacques Hamilton-Dutoit,1 Torben Steiniche1 1
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark 2 Danish Cancer Society Research Center, Copenhagen, Denmark 3 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Correspondence to Johanne Lade Keller, Institute of Pathology, Aarhus University Hospital, Noerrebrogade 44, Aarhus C DK-8000, Denmark; [email protected] Received 10 December 2013 Revised 2 February 2014 Accepted 6 February 2014 Published Online First 7 March 2014
ABSTRACT 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
Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker Johanne Lade-Keller,1 Rikke Riber-Hansen,1 Per Guldberg,2 Henrik Schmidt,3 Stephen Jacques Hamilton-Dutoit,1 Torben Steiniche1 1
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark 2 Danish Cancer Society Research Center, Copenhagen, Denmark 3 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Correspondence to Johanne Lade Keller, Institute of Pathology, Aarhus University Hospital, Noerrebrogade 44, Aarhus C DK-8000, Denmark; [email protected] Received 10 December 2013 Revised 2 February 2014 Accepted 6 February 2014 Published Online First 7 March 2014
ABSTRACT 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
