Abstract
Purpose: :
To gain insight into the mechanisms which underlie metastasis formation and growth in uveal melanoma by comparing gene expression patterns between primary uveal melanomas and liver metastasis from uveal melanoma.
Methods: :
Seven primary uveal melanomas and seven liver metastases from uveal melanoma were included in the study. Microarray analysis was performed using a spotted oligonucleotide microarray containing 36,000 features and by applying a reference sample study design. Genes with metastasis associated expression pattern were identified using the Significance Analysis for Microarray (SAM) algorithm. Primary tumors and metastasis were characterized in terms of cell type (by conventional histology), microcirculation patterns (on PAS stained sections), proliferative activity of tumor cells (using Ki–67 immunostaining), and apoptosis rate (on TUNEL stained sections).
Results: :
Microarray analysis identified 193 features that showed metastasis associated expression pattern at the False Discovery Rate (FDR) level of 0%. Nine of these features showed increased mRNA levels in metastasis compared with primary tumors while 184 showed decreased mRNA levels in metastasis. Consistent with findings from other cancer types, genes which show increased expression in metastasis are involved in protein synthesis. Genes which show decreased expression in metastasis belongs to variety of functional classes. SAM assessment and hierarchical clustering revealed that gene expression patterns differ between primary and metastatic lesion significantly more than across tumors classified according to prognostic factors such as microcirculation patterns and cell type.
Conclusions: :
Multiple genes show altered expression patterns in liver metastasis from uveal melanoma compared with primary uveal melanoma. Further studies will demonstrate the potential role of these genes in the development and growth of such liver metastasis.
Keywords: melanoma • gene microarray • choroid