Poly(ADP-ribose) in the skin and in melanomas
Zsuzsanna Géhl1,2*, Péter Bai1,3*, Edina Bodnár4, Gabriella Emri4, Éva Remenyik4, János Németh2, Pál Gergely1,3, László Virág1,3 and Éva Szabó4
1Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, 2Semmelweis University, Department of Ophthalmology, Budapest, Hungary, 3Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary and 4Department of Dermatology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
*These authors contributed equally to the work.
Offprint requests to: László Virág M.D. D.Sc., Department of Medical Chemistry, University of Debrecen, MHSC, Nagyerdei krt 98. H-4032 Debrecen, Hungary, e-mail: lvirag@med.unideb.hu
Summary. Cutaneous melanoma (CM) and uveal melanoma (UM) represent the most aggressive pigment cell tumor types. Our investigation examined the signaling molecule poly(ADP-ribose) (PAR) in CM and UM. We have demonstrated PAR in keratinocytes, sebocytes, hair follicles, endothelial cells and in subcutaneous adipocytes in the normal skin indicating that PAR may regulate physiological functions in these cell types. Furthermore, CM cells were PAR positive and tumor invasion level/thickness of CM correlated with the PAR content of the cell nuclei, with higher Clark and Breslow indices and AJCC scores associating with higher PAR content. This correlation was especially marked in the samples of female patients. In UM tumors (n=12) a slight overall and strong perivascular PAR staining was observed with considerable individual variations. In view of recent successful clinical trials with PARP inhibitors as adjuvant chemotherapeutic agents, our results suggest that melanomas may display differential sensitivity towards this novel therapeutic modality which should be considered for the selection of patients. Histol Histopathol 27, 651-659 (2012)
Key words: Melanoma, Poly(ADP-ribose), Poly(ADP-ribose) polymerase, Skin
DOI: 10.14670/HH-27.651