Chromosome 3 Aberrations Precede the Development of Network Extravascular Matrix Pattern in Uveal Melanoma

Abstract

Purpose:: Monosomy of chromosome 3 and network extravascular matrix patterns are associated with death of uveal melanoma (UM) patients. Networks are typically found in confined area within the tumor while the intratumor distribution of chromosome 3 aberrations is unknown. We aim to assess the spatial correlation among chromosome 3 aberrations and networks in UM.

Methods:: Extravascular matrix patterns, proliferative activity, and cell type were characterized in 15 primary UM. Cells were isolated using laser capture microdissection (LCM) from two tumor regions and one normal retina area from each tissue block. In the eight tumors containing networks cells were microdissected from one area with networks and another area without networks. In seven tumors without networks cells were microdissected from two distinct tumor areas. Presence of chromosome 3 aberrations was assessed using microsatellite analysis in each LCM sample (MSA).

Results:: Useful MSA data was obtained from 43 of the 45 samples. Monosomy 3 was detected in 16 samples from eight tumors. There was no intratumor heterogeneity in terms of monosomy 3 regardless of existence of heterogeneity in terms of networks, cell type, or proliferative activity across the two samples from the same tumor. Networks were associated with monosomy 3 on the whole tumor level (p = 0.005)

Conclusions:: While monosomy 3 is associated with network pattern it does not account for intratumor heterogeneity in terms of network pattern location. Thus, monosomy 3 aberrations precede the development of network patterns and may contribute but are not sufficient for its development.

Keywords: melanoma • tumors