Heat shock protein expression in the eye and in uveal melanoma.
OBJECTIVE
Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types, whereas HSPs may also have clinical use as stimulators in tumor vaccination. HSP expression levels were determined in normal eyes and in uveal melanoma and tested whether HSPs expression was associated with prognostic parameters in the uveal melanoma.


METHODS
Expression of HSP27, HSP70, HSP90, and glycoprotein96 (GP96) were determined on paraffin-embedded and frozen sections from seven healthy eyes, 20 primary uveal melanomas without prior treatment, and 18 uveal melanomas after prior treatment. HSP expression was determined by alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemistry, using appropriate monoclonal antibodies and scored semiquantitatively. Expression of HSPs was validated on retinal tissue of a normal eye and in two uveal melanoma cell lines by Western blot analysis.


RESULTS
Expression of HSPs was observed in epithelial and pigment cells of the normal eyes. In uveal melanoma, the level of expression of HSPs varied. Expression of HSP27 and GP96 was noted in more than 30 of 38 uveal melanomas (with, respectively, a mean of 66% and 53% positive cells). HSP70 and HSP90 were expressed in 6% of tumor cells. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors. There was not a significant difference in expression of the HSPs between uveal melanomas with or without any type of prior treatment.


CONCLUSIONS
In this study, expression of HSPs in uveal melanoma is not correlated with known histopathologic prognostic factors. The high expression of GP96 indicates that this protein is a potential vector in tumor vaccination in patients with large uveal melanomas.
Missotten
Guy S
GS
Department of Ophthalmology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands. g.s.o.a.missotten@lumc.nl
Journée-de Korver
Johanna G
JG
de Wolff-Rouendaal
Didi
D
Keunen
Jan E
JE
Schlingemann
Reinier O
RO
Jager
Martine J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D005123:Eye / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008875:Middle Aged; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C052646:sarcoma glycoprotein gp96 rejection antigens