PMID- 24005052
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20211021
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 134
IP  - 3
DP  - 2014 Mar
TI  - Prognostic impact of PHIP copy number in melanoma: linkage to ulceration.
PG  - 783-790
LID - 10.1038/jid.2013.369 [doi]
AB  - 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.
FAU - Bezrookove, Vladimir
AU  - Bezrookove V
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - De Semir, David
AU  - De Semir D
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Nosrati, Mehdi
AU  - Nosrati M
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Tong, Schuyler
AU  - Tong S
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Wu, Clayton
AU  - Wu C
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Thummala, Suresh
AU  - Thummala S
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Dar, Altaf A
AU  - Dar AA
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Leong, Stanley P L
AU  - Leong SPL
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Cleaver, James E
AU  - Cleaver JE
AD  - UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
FAU - Sagebiel, Richard W
AU  - Sagebiel RW
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Miller, James R 3rd
AU  - Miller JR 3rd
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
FAU - Kashani-Sabet, Mohammed
AU  - Kashani-Sabet M
AD  - Center for Melanoma Research and Treatment, California Pacific Medical Center and 
      Research Institute, San Francisco, California.
LA  - eng
GR  - R01 CA114337/CA/NCI NIH HHS/United States
GR  - R01 CA122947/CA/NCI NIH HHS/United States
GR  - CA114337/CA/NCI NIH HHS/United States
GR  - CA122947/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130904
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (PHIP protein, human)
SB  - IM
CIN - J Invest Dermatol. 2014 Mar;134(3):600-2. PMID: 24518113
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Biomarkers, Tumor/genetics
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Dosage/genetics
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Melanoma/*genetics/mortality/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Neoplasm Transplantation
MH  - Prognosis
MH  - Skin Neoplasms/*genetics/mortality/pathology
MH  - Skin Ulcer/*genetics/mortality/pathology
PMC - PMC3945648
MID - NIHMS520227
EDAT- 2013/09/06 06:00
MHDA- 2014/04/10 06:00
PMCR- 2014/09/01
CRDT- 2013/09/06 06:00
PHST- 2013/04/11 00:00 [received]
PHST- 2013/08/11 00:00 [revised]
PHST- 2013/08/12 00:00 [accepted]
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - S0022-202X(15)36675-6 [pii]
AID - 10.1038/jid.2013.369 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2014 Mar;134(3):783-790. doi: 10.1038/jid.2013.369. Epub 2013 
      Sep 4.