Abstract
AimsTo determine the expression of breast metastasis suppressor 1 (BRMS1) in human uveal melanoma (UM) tissues and cell lines. In addition, we intend to establish a possible association between BRMS1 expression and the presence of metastatic disease.MethodsThirty-one formalin-fixed paraffin-embedded tissues from enucleated eyes of patients with UM were immunostained. Clinical–pathological data were obtained, including age, tumour location, largest dimension, cell type, and occurrence of metastasis. The expression of BRMS1 mRNA in four human UM cell lines was determined by real-time reverse transcriptase polymerase chain reaction, and protein expression was assessed by immunocytochemistry and western blot. The association between BRMS1 immunostaining and location, largest tumour dimension, and tumour cell type was determined using the correlation coefficient test. The association between BRMS1 immunostaining and the incidence of metastasis was assessed using Kaplan–Meier analysis.ResultsOf the 31 cases of UM, 24 (77.42%) stained positive and seven (22.58%) negative for BRMS1. From the positively stained tumours, 21 (87.50%) showed cytoplasmatic staining. Macrophages were usually positive when present in the tumour and staining intensity was generally higher than in UM cells. BRMS1 mRNA was present in all four human UM cell lines, as well as cytoplasmatic immunoexpression of BRMS1. Immunoblotting showed variable BRMS1 protein levels between the different cell lines. No statistically significant correlation was found between BRMS1 protein expression and survival (P = 0.69), tumour cell type (P = 0.68), largest tumour dimension (P = 0.75), and tumour location (P = 0.11).ConclusionsBRMS1 is expressed in UM both at the mRNA and protein level; however, neither was associated with any of the prognosticor outcome parameters that we tested.
Highlights
Uveal melanoma (UM) represents approximately 5% of all reported melanomas [1], with an incidence of five to seven cases per million people per year [2]
The reverse transcriptase polymerase chain reaction (RT-PCR) showed that the breast metastasis suppressor 1 (BRMS1) mRNA was present in the four human UM cell lines
In human breast carcinoma cell lines, for example, it was shown that the amount of BRMS1 mRNA present in the cell lines is inversely correlated with their metastatic potential [20]
Summary
Uveal melanoma (UM) represents approximately 5% of all reported melanomas [1], with an incidence of five to seven cases per million people per year [2]. Despite improvements in diagnosis and treatment of the primary tumour [3,4,5,6,7], the survival rate of patients has remained relatively unchanged for the past few decades [8, 9]. The traditional concept that metastasis occurs during late stages of tumourigenesis [10] has been replaced by evidence showing early tumour cell dissemination and metastatic disease developing in parallel with the primary tumour [17]. Callejo et al [18] recorded the presence of circulating malignant cells in patients with UM at the time of diagnosis despite the size of the primary tumour, indicating that UM is a cancer that metastasizes early
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