| Author |
Bezrookove, Vladimir De Semir, David Nosrati, Mehdi Tong, Schuyler Wu, Clayton Thummala, Suresh Dar, Altaf A. Leong, Stanley P. L. Cleaver, James E. Sagebiel, Richard W. Miller, James R. Kashani-Sabet, Mohammed |
| Description |
Country affiliation: United States Author Affiliation: Bezrookove V ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); De Semir D ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Nosrati M ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Tong S ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Wu C ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Thummala S ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Dar AA ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Leong SP ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Cleaver JE ( UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.); Sagebiel RW ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Miller JR ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.); Kashani-Sabet M ( Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California, USA.) |
| Abstract |
Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced distant metastasis-free survival (DMFS; P=0.01) and disease-specific survival (DSS; P=0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P=0.03) and DSS (P=0.03). Increased PHIP copy number was an independent predictor of ulceration status (P=0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P<0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of lactate dehydrogenase 5, hypoxia-inducible factor 1 alpha subunit, and vascular endothelial growth factor, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. |
| Subject Keyword |
Discipline Dermatology Intracellular Signaling Peptides And Proteins Genetics Melanoma Skin Neoplasms Skin Ulcer Animals Tumor Markers, Biological Cell Line, Tumor Gene Dosage Kaplan-meier Estimate Mortality Pathology Mice Mice, Nude Neoplasm Transplantation Prognosis Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
