Abstract
Purpose: :
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite progress in diagnosis and treatment of the primary tumor, the survival rate has remained unchanged for decades. Nearly half of the patients develop metastasis to the liver within 10 years of the primary diagnosis. BRMS1 is a metastasis suppressor gene (MSG) that has been shown to suppress metastasis in many tumors. The purpose of this study was to investigate the expression of BRMS1 in UM and determine possible correlations between this expression and survival rate of patients along with a number of known prognostic factors.
Methods: :
The expression level of BRMS1 mRNA in four human UM cell lines was determined by quantitative real-time PCR. Protein expression in these cell lines was assessed by immunocytochemistry and western blot. Additionally, sections from 31 formalin-fixed, paraffin-embedded, primary human UM specimens were immunostained. Clinical-pathological data was obtained. The association between the immunoexpression and tumor location, largest tumor dimension and tumor cell type was determined using the correlation coefficient test. The Kaplan-Meier survival analysis was used to assess the association between immunostaining and the incidence of metastasis.
Results: :
BRMS1 mRNA was detected in the four cell lines. Cytoplasmatic staining of BRMS1 was evident in all cell lines with no discernible difference in staining intensity. Immunoblotting showed variable BRMS1 protein levels between the cell lines. Of the 31 cases of UM studied, 24 (77.42%) were positive and seven (22.58%) were negative for BRMS1. From the positively stained tumors, twenty-one (87.50%) demonstrated cytoplasmatic staining. Tumor infiltrating macrophages were generally positive when present and their staining intensity was often higher than that of UM cells. No statistically significant correlation was seen between BRMS1 protein expression and survival, tumor cell type, largest tumor dimension and tumor location.
Conclusions: :
To the best of our knowledge, this is the first study assessing the MSG BRMS1 in UM. It was shown that BRMS1 is expressed at the mRNA and protein levels in UM. The majority of the specimens that stained revealed a cytoplasmatic staining, which can possibly be explained by one of BRMS1’s mechanisms of action. Further studies are required to better elucidate our findings of macrophage staining. In addition, no statistically significant correlation could be established between BRMS1 protein expression and survival, tumor cell type, largest tumor dimension and tumor location.
Keywords: melanoma • tumors • gene/expression