PMID- 19643972
OWN - NLM
STAT- MEDLINE
DCOM- 20100203
LR  - 20220408
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 51
IP  - 1
DP  - 2010 Jan
TI  - Proteomics of uveal melanomas suggests HSP-27 as a possible surrogate marker of 
      chromosome 3 loss.
PG  - 12-20
LID - 10.1167/iovs.09-3913 [doi]
AB  - PURPOSE: To compare the proteomic profiles of primary uveal melanomas, with and 
      without loss of chromosome 3. METHODS: Frozen specimens from three uveal 
      melanomas with disomy 3 and from four tumors with monosomy 3, according to 
      fluorescence in situ hybridization (FISH) analysis, were subjected to 
      high-resolution, two-dimensional (2-D) gel electrophoresis. The protein 
      expression profiles of the two uveal melanoma cytogenetic groups were compared: 
      Proteins that differed significantly were excised and analyzed by tandem mass 
      spectrometry. Differentially expressed proteins were further analyzed with 
      Western blot analysis. An independent cohort of 41 formalin-fixed, 
      paraffin-embedded (FFPE) uveal melanomas, whose chromosome 3 status had been 
      determined by multiplex ligation-dependent probe amplification (MLPA), was 
      examined for the appropriate antigens by immunohistochemistry. RESULTS: Four 
      protein spots were 1.5-fold (Student's t-test, P < 0.05) differentially expressed 
      in the two uveal melanoma types: two spots were overexpressed in the disomy 3 
      group compared with the monosomy 3 group, whereas two spots were underexpressed. 
      Identification of the four spots yielded nine proteins. Western blot analysis 
      confirmed the results for heat shock protein (HSP)-27, vimentin, and pyruvate 
      dehydrogenase beta (PDHB), with a statistical significance for the first two 
      proteins. HSP-27 was significantly downregulated, whereas vimentin was 
      upregulated in the monosomy 3 tumors (Student's t-test, P = 0.003 and P = 0.005, 
      respectively). Immunohistochemistry confirmed low-to-negative HSP-27 protein 
      expression in monosomy 3 uveal melanomas (Student's t-test; P = 0.011). 
      CONCLUSIONS: Low-to-negative HSP-27 protein expression in uveal melanoma 
      correlates strongly with monosomy 3. Further validation is necessary to determine 
      whether immunohistochemical assessment of HSP-27 expression correlates with 
      metastatic mortality.
FAU - Coupland, Sarah E
AU  - Coupland SE
AD  - Department of Pathology, School of Cancer Studies, University of Liverpool, 
      Liverpool, United Kingdom. s.e.coupland@liverpool.ac.uk
FAU - Vorum, Henrik
AU  - Vorum H
FAU - Mandal, Nakul
AU  - Mandal N
FAU - Kalirai, Helen
AU  - Kalirai H
FAU - Honore, Bent
AU  - Honore B
FAU - Urbak, Steen Fiil
AU  - Urbak SF
FAU - Lake, Sarah L
AU  - Lake SL
FAU - Dopierala, Justyna
AU  - Dopierala J
FAU - Damato, Bertil
AU  - Damato B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090730
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HSP27 Heat-Shock Proteins)
RN  - 0 (Vimentin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*metabolism
MH  - Blotting, Western
MH  - Chromosomes, Human, Pair 3/*genetics
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Female
MH  - HSP27 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Melanoma/*genetics/*metabolism
MH  - Middle Aged
MH  - *Monosomy
MH  - Proteomics
MH  - Uveal Neoplasms/genetics/*metabolism
MH  - Vimentin/metabolism
EDAT- 2009/08/01 09:00
MHDA- 2010/02/04 06:00
CRDT- 2009/08/01 09:00
PHST- 2009/08/01 09:00 [entrez]
PHST- 2009/08/01 09:00 [pubmed]
PHST- 2010/02/04 06:00 [medline]
AID - iovs.09-3913 [pii]
AID - 10.1167/iovs.09-3913 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2010 Jan;51(1):12-20. doi: 10.1167/iovs.09-3913. Epub 
      2009 Jul 30.