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Published on: September 7, 2011
The spatial distribution of monosomy 3 and network vasculogenic mimicry patterns in uveal melanoma
Tal Meir1, Michael Zeschnigk, Lars Masshöfer
1Department of Ophthalmology, Hadassah-Hebrew University Medical Center and The Hebrew University School of Medicine, Jerusalem, Israel.
Purpose:
Monosomy of chromosome 3 and network vasculogenic mimicry patterns are associated with death in patients with uveal melanoma (UM). Networks are typically found in confined areas within the tumor, whereas the intratumor distribution of chromosome 3 aberrations is unknown. This study was conducted to assess the spatial correlation among chromosome 3 aberrations and networks in UM.
Methods:
Vasculogenic mimicry patterns, proliferative activity, and cell type were characterized in 15 enucleated eyes with primary UM. Cells were isolated by laser capture microdissection (LCM) from two tumor regions and one normal retina area from each tissue block. In the eight tumors containing networks, the cells were microdissected from one area with networks and a different area without networks. In seven tumors without networks, cells were microdissected from two distinct tumor areas. The presence of chromosome 3 aberrations was assessed by microsatellite analysis (MSA) in each LCM sample.
Results:
Useful MSA data was obtained from 43 of the 45 samples. Monosomy 3 was detected in 16 samples of eight tumors. There was no intratumor heterogeneity for monosomy 3, regardless of the existence of heterogeneity in networks, cell type, or proliferative activity across the two samples from the same tumor. Networks were associated with the presence of monosomy 3 throughout the entire tumor (P = 0.02).
Conclusions:
Of the histologic prognostic factors of metastasis in UM studied, only the presence of a network vasculogenic mimicry pattern but not its location is associated with monosomy 3. This suggests that monosomy 3 may contribute to but is not sufficient for the development of the network pattern.
Insights
Monosomy 3 is present throughout uveal melanoma tumors with network vasculogenic mimicry. This finding suggests monosomy 3 contributes to network formation but is not sufficient on its own.
Area of Science:
- Ophthalmology
- Oncology
- Genetics
Background:
- Monosomy of chromosome 3 and network vasculogenic mimicry (VMN) are linked to poor prognosis in uveal melanoma (UM).
- The spatial distribution of chromosome 3 aberrations within UM tumors remains largely unknown.
- VMN are typically observed in localized tumor regions.
Purpose of the Study:
- To investigate the spatial correlation between chromosome 3 aberrations and VMN in UM.
- To determine if monosomy 3 exhibits intratumor heterogeneity.
Main Methods:
- Fifteen primary UM tissues were analyzed.
- Laser capture microdissection (LCM) isolated cells from tumor areas with and without VMN, and normal retina.
- Microsatellite analysis (MSA) assessed chromosome 3 aberrations in LCM samples.
Main Results:
- Monosomy 3 was detected in 16 samples across eight UM tumors.
- No intratumor heterogeneity for monosomy 3 was observed.
- VMN were significantly associated with the presence of monosomy 3 throughout the tumor (P = 0.02).
Conclusions:
- The presence of VMN, not its specific location, is associated with monosomy 3 in UM.
- Monosomy 3 may play a role in, but is not solely sufficient for, the development of VMN.
