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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.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.Heat shock protein 27 score was lower in monosomy 3 melanomas than in disomy 3 tumours (p < 0.001; Mann–WhitneyU-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.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.