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S. E. Coupland, H. Kalirai, B. Damato; Loss of hsp27 Protein Expression correlates with Monosomy 3 in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3388.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) causes death from hepatic metastasis in approximately 50% of all patients, despite successful treatment of the primary tumor. Currently, the strongest predictor for metastatic death is chromosome 3 loss. We previously performed proteomic analysis of monosomy 3 (M3) versus disomy 3 (D3) UMs in collaboration with Dr H Vorum, Denmark, and found reduced expression of the heat shock protein, hsp27 in M3 compared with D3 tumors. This is consistent with hsp27 over-expression as an indicator of good prognosis in ovarian and non small cell lung carcinomas. In vitro studies in cutaneous melanoma have related this effect to an inhibition of cell proliferation and reduced invasiveness of the cells due to reduced secretion of matrix metalloproteinases. The aim of this study was to validate these findings by immunohistochemistry (IHC) in a larger cohort of patients.
IHC analysis of hsp27 protein expression was performed in 11 patients with M3 and 24 patients with D3, the chromosome 3 status having been determined by fluorescence in situ hybridization and/or multiplex ligation-dependent probe amplification. Patients with D3 were further subdivided according to whether or not they died from metastatic disease (13 and 11 patients respectively). Staining was scored as the percentage of hsp27-positive tumor cells in paraffin-embedded, formalin-fixed sections as assessed by two independent observers. The percentage of hsp27 +ve cells was categorized as: (1) 0-20% (2) 21-70% (3) >70%.
In all positive tumor cells, hsp27 staining was cytoplasmic and did not correlate with spindle or epithelioid melanoma cell type. Hsp27 was absent from tumor cells surrounding blood vessels. Tumors with low proportions of hsp27 +ve cells were significantly more likely to be of monosomy 3 type (student t-test, p≤0.005).
Low to negative hsp27 protein expression in UM correlates strongly with M3. Our preliminary results need to be validated by larger studies to determine whether measurement of hsp27 expression by IHC can reliably identify highly-lethal UMs when cytogenetic studies are not possible.
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