Uveal Melanomas Show Tumor Heterogeneity for Chromosome 3; Consequences for FNAB's

Abstract

 

Purpose:

 

Monosomy 3 is a significant indicator of poor prognosis in uveal melanoma. Nowadays, fine needle aspiration biopsies (FNAB's) are used to detect the presence of monosomy 3, allowing early monitoring of patients at high risk for metastatic disease. This application of FNAB’s is based on the assumption that uveal melanomas are homogeneous for chromosome 3 aberrations. To test this assumption, we studied the homogeneity of uveal melanomas and tried to identify the best technique to recognize monosomy 3 in a series of 50 enucleated uveal melanomas.

 

Methods:

 

We performed cytogenetic analysis and fluorescence in situ hybridization (FISH) for monosomy 3 on cultured cells of uveal melanomas obtained by enucleation. The percentage of tumor cells with monosomy 3 was assessed with FISH on nuclei isolated from paraffin–embedded tissue, using a DNA–specific probe for the centromere region of chromosome 3.

 

Results:

 

Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) tumors. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least seven cases. However, heavy tumor pigmentation and large areas of necrosis obstructed analysis of FISH signals in most other tumors. FISH on nuclei isolated from paraffin embedded–tissue was possible in all cases and showed monosomy 3 in 31 (62%) of the uveal melanomas studied.

 

Conclusions:

 

FISH analysis on paraffin sections showed that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin–embedded tissue shows a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cell cultures. These findings have major implications for interpreting the results of FNAB's.  

 

Keywords: melanoma • fluorescent in situ hybridization • genetics