Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution
Abstract
:1. Introduction
2. Results
2.1. A High MVD Relates to a Mixed/Epithelioid Cell Type and a Worse Clinical Outcome
2.2. MVD Relates to the Expression of Several Angiogenesis-Related Genes
2.3. MVD Relates to Increased Numbers of Macrophages (CD68+) as Well as T Cells (CD4+)
2.4. MVD Relates to Monosomy 3 and BAP1 Loss, but Not to Gain of Chromosome 8q
2.5. Expression of Angiogenesis-Related Genes Is Related to Genetic Progression of UM
3. Discussion
4. Materials and Methods
4.1. Patient Selection
4.2. Histopathology
4.3. Immunohistochemistry and Immunofluorescence
4.4. Chromosome 3/8q Status and Gene Expression
4.5. TCGA Data
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Categorical | Total | MVD | p-Value |
---|---|---|---|
Cases (%) | Median | ||
Gender | |||
Male | 23 (53) | 89.0 | 0.85 # |
Female | 20 (47) | 88.5 | |
Side | |||
OD | 23 (53) | 86.0 | 0.95 # |
OS | 20 (47) | 93.5 | |
TNM stage (8th) | |||
T1 | 4 (9) | 79.0 | 0.23 * |
T2 | 14 (33) | 82.0 | |
T3 | 25 (58) | 91.0 | |
Pigmentation | |||
Light | 29 (67) | 89.0 | 0.97 # |
Dark | 14 (33) | 96.5 | |
Cell Type | |||
Spindle | 11 (26) | 69.0 | 0.009 # |
Mixed + Epithelioid | 32 (74) | 100.0 | |
Ciliary Body Involvement | |||
No | 24 (56) | 89.0 | 0.58 # |
Yes | 19 (44) | 103.0 | |
Loops and Networks | |||
None | 7 (16) | 71.0 | 0.052 * |
Loops+, networks− | 8 (19) | 83.0 | |
Loops+, networks+ | 27 (63) | 102.0 | |
Metastasis | |||
No | 25 (58) | 76.0 | 0.010 # |
Yes | 18 (42) | 110.0 | |
Melanoma-Related Death | |||
No | 25 (58) | 76.0 | 0.010 # |
Yes | 18 (42) | 110.0 | |
NUMERICAL | Total | Correlation | p-Value |
Spearman | |||
Age—Median | 63.6 | 0.135 | 0.390 |
LBD—Median | 13.0 | 0.299 | 0.051 |
Prominence—Median | 8.0 | −0.278 | 0.072 |
mRNA | Median (Range) | Spearman Corr. | p-Value |
---|---|---|---|
VEGF-A | 6.76 (6.51–7.34) | 0.005 | 0.989 |
VEGF-B | 8.54 (7.6–9.41) | −0.425 | 0.024 * |
VEGF-C | 6.73 (6.37–7.73) | 0.209 | 0.286 |
HIF1A | 7.21 (6.89–7.91) | 0.327 | 0.089 |
VHL | 7.96 (7.35–8.54) | −0.226 | 0.248 |
ANGPT1 | 6.57 (6.31–7.04) | 0.155 | 0.431 |
ANGPT2 | 6.54 (6.23–8.19) | 0.389 | 0.041 * |
PDGFA | 6.96 (6.46–7.82) | 0.060 | 0.761 |
CD34 | 7.37 (6.73–7.9) | 0.497 | 0.007 * |
CDH1 | 10.74 (5.8–12.94) | 0.337 | 0.079 |
PECAM1 | 7.23 (6.68–9.57) | 0.367 | 0.055 |
VWF | 9.86 (8.62–11.14) | 0.479 | 0.010 * |
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Share and Cite
Brouwer, N.J.; Gezgin, G.; Wierenga, A.P.A.; Bronkhorst, I.H.G.; Marinkovic, M.; Luyten, G.P.M.; Versluis, M.; Kroes, W.G.M.; van der Velden, P.A.; Verdijk, R.M.; et al. Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution. Cancers 2019, 11, 979. https://doi.org/10.3390/cancers11070979
Brouwer NJ, Gezgin G, Wierenga APA, Bronkhorst IHG, Marinkovic M, Luyten GPM, Versluis M, Kroes WGM, van der Velden PA, Verdijk RM, et al. Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution. Cancers. 2019; 11(7):979. https://doi.org/10.3390/cancers11070979
Chicago/Turabian StyleBrouwer, Niels J., Gülçin Gezgin, Annemijn P.A. Wierenga, Inge H.G. Bronkhorst, Marina Marinkovic, Gregorius P.M. Luyten, Mieke Versluis, Wilma G.M. Kroes, Pieter A. van der Velden, Robert M. Verdijk, and et al. 2019. "Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution" Cancers 11, no. 7: 979. https://doi.org/10.3390/cancers11070979