HSP-27 protein expression in uveal melanoma: correlation with predicted survival.
OBJECTIVE
Almost 40% of uveal melanomas (UM) are fatal, because of metastatic disease that usually involves the liver. Partial or complete deletion of chromosome 3 (i.e., monosomy 3) is a strong predictor of metastatic mortality; however, genetic analysis is not always possible. The aim of this study was to determine whether heat shock protein 27 (HSP-27) protein expression could reliably predict prognosis.


METHODS
Immunohistochemical analysis of HSP-27 protein expression was performed on formalin-fixed, paraffin-embedded sections from 99 UM of known chromosome 3 status, as determined by multiplex ligation-dependent probe amplification. Slides were evaluated blind by three independent observers. The percentage of tumour cells staining for HSP-27 was categorized as: 0 (<1%); 1 (1-24%); 2 (25-49%); 3 (50-74%) or 4 (>74%). The staining intensity was categorized as: 0 (no staining); 1 (weak); 2 (moderate) and 3 (strong). These two categories were multiplied together to obtain the HSP-27 expression score. All data were processed in spss for statistical analyses.


RESULTS
Heat shock protein 27 score was lower in monosomy 3 melanomas than in disomy 3 tumours (p<0.001; Mann-Whitney U-test). An 'accelerated failure time model' was used to generate predicted survival for all patients included in the study. Kaplan-Meier analysis indicated a significantly decreased predicted 8-year survival rate for patients with an HSP-27 Score≤6 (p=0.03; Log rank test). Predicting monosomy 3 was enhanced by considering the HSP-27 score together with basal tumour diameter, melanoma cytomorphology and mitotic rate.


CONCLUSIONS
Low HSP-27 expression correlates with monosomy 3 in UM and with increased predicted mortality. When assessed together with other clinical and pathological variables, the HSP-27 score enhances estimation of survival probability.
Division of Pathology, School of Cancer Studies, University of Liverpool, Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, UK.
Fidan
F
Jmor
Helen
H
Kalirai
Azzam
A
Taktak
Bertil
B
Damato
Sarah E
SE
Coupland
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D008875:Middle Aged; D018832:Molecular Chaperones; D009006:Monosomy / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D055815:Young Adult
D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones