Nestin expression in primary and metastatic uveal melanoma

Abstract

PurposeNestin, a member of the intermediate filament protein family, has been described as a putative cancer stem cell marker (CSC) in a variety of tumours. In particular, increased Nestin expression is associated with an aggressive and primitive tumour phenotype as well as a poor prognosis in cutaneous melanoma. In this study, we examined the expression of nestin in primary (PUM) and metastatic uveal melanoma (MUM) samples, and correlated the findings with histological, clinical and survival data.MethodsNestin expression was assessed by immunohistochemistry in 141 PUM and 26 MUM samples; 11 of the PUM cases were matched with their corresponding metastases. The percentage of tumour cells staining positively for nestin was scored by three independent observers. Statistical analysis of all data was performed with SPSSResultsIncreased levels of nestin in PUM samples were associated with known poor prognostic parameters, including epithelioid cells (p < 0.001), closed loops (p = 0.001),increased mitotic count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001). Positive staining was identified in both the cytoplasm and membrane of tumour cells. PUM with nestin expression levels above a cut‐off value of 10% (as determined by ROC analysis) were associated with a significantly reduced survival time (Log rank, p = 0.002). In the MUM, a higher nestin percentage combined with poor prognostic markers led to a shorter survival time following the development of metastases.ConclusionsIn conclusion, increased nestin expression in PUM is an independent predictor of a tumour phenotype associated with metastatic progression and reduced survival time at metastasis.