Abstract
Background: VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 are important proteins involved in the induction and development of a new blood vessel network through which the tumor is properly nourished and oxygenated.
Objectives: The aim of the study was to evaluate changes in VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 expression in endometrial cancer depending on its grade and to determine the VEGFR-1 to VEGFR-2 concentration ratio.
Methods: The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, Cracow, Poland). It included the one-way ANOVA and Tukey's post-hoc test (p<0.05).
Results: Statistically significant differences in the level of VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 were observed between the majority of analyzed groups (except for VEGF-B; G3 vs. G1, p=0.997700). The expression pattern of VEGF-A, VEGF-R1, VEGFR-2 was as follows: G3>G2>G1>C; VEGF-B: G2> G3> G1>C. A lower concentration of VEGFR-1 than VEGFR-2 was found regardless of the cancer grade.
Conclusion: VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 are key proteins involved in tumor angiogenesis. The analysis of the entire panel of proteins participating in a given process is an important element of modern diagnostics. The concentration ratio of VEGFR-1 to VEGFR-2 appears to be a determining factor in the patients' survival prognosis.
Keywords: VEGF-A/B, VEGFR-1/2, angiogenesis, endometrial cancer, tumor angiogenesis, adenomyosis.
Graphical Abstract
[http://dx.doi.org/10.1002/0470035439.ch2]
[http://dx.doi.org/10.1038/nrc1093] [PMID: 12778130]
[http://dx.doi.org/10.1007/s10555-007-9094-7] [PMID: 17717633]
[http://dx.doi.org/10.1016/j.semcancer.2010.06.004] [PMID: 20599506]
[http://dx.doi.org/10.1007/s00418-008-0527-3] [PMID: 18953558]
[http://dx.doi.org/10.1097/CCO.0b013e32831bed7e] [PMID: 19125020]
[http://dx.doi.org/10.1002/path.1355] [PMID: 14517833]
[http://dx.doi.org/10.1101/cshperspect.a006502] [PMID: 22762016]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1520] [PMID: 16951216]
[http://dx.doi.org/10.1084/jem.20100438] [PMID: 21098094]
[http://dx.doi.org/10.1084/jem.20111424] [PMID: 22393126]
[http://dx.doi.org/10.1158/2159-8290.CD-12-0085] [PMID: 22777769]
[http://dx.doi.org/10.1016/j.yexcr.2005.11.012] [PMID: 16336962]
[http://dx.doi.org/10.1134/S0006297908070031] [PMID: 18707583]
[http://dx.doi.org/10.1056/NEJMra0706596] [PMID: 18463380]
[http://dx.doi.org/10.3389/fcvm.2018.00039] [PMID: 29732375]
[http://dx.doi.org/10.1007/s10456-017-9552-y] [PMID: 28361267]
[http://dx.doi.org/10.29252/mlj.12.4.1]
[http://dx.doi.org/10.1073/pnas.0813061106] [PMID: 19369214]
[http://dx.doi.org/10.2147/vhrm.2006.2.2.97] [PMID: 17319453]
[http://dx.doi.org/10.3892/mmr.2017.6868] [PMID: 28656251]
[http://dx.doi.org/10.2174/1389201019666180730094046] [PMID: 30058482]
[http://dx.doi.org/10.1186/s40661-017-0056-7] [PMID: 29214032]
[http://dx.doi.org/10.1016/j.bbrc.2008.07.121] [PMID: 18680722]
[http://dx.doi.org/10.1038/nrc2524] [PMID: 19029957]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1405] [PMID: 19223554]
[http://dx.doi.org/10.1038/nrc2444] [PMID: 18633355]
[http://dx.doi.org/10.3233/CBM-2007-3606] [PMID: 18048970]
[http://dx.doi.org/10.1158/1078-0432.CCR-0946-03] [PMID: 15623639]
[http://dx.doi.org/10.1038/sj.bjc.6601194] [PMID: 12942123]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1017] [PMID: 18094433]
[http://dx.doi.org/10.1371/journal.pone.0184576] [PMID: 28991928]
[http://dx.doi.org/10.1016/j.ygyno.2005.05.003] [PMID: 15982726]
[http://dx.doi.org/10.1002/(SICI)1097-0142(19960801)78:3<454: AID-CNCR12>3.0.CO;2-Y] [PMID: 8697391]
[http://dx.doi.org/10.1002/path.1339] [PMID: 12754739]
[http://dx.doi.org/10.1634/theoncologist.2015-0221] [PMID: 26446239]
[http://dx.doi.org/10.3892/ol.2015.3415] [PMID: 26622771]
[http://dx.doi.org/10.1186/bcr3354] [PMID: 23146280]
[http://dx.doi.org/10.1002/cncr.24193] [PMID: 19197998]
[http://dx.doi.org/10.1371/journal.pone.0064186] [PMID: 23704979]
[http://dx.doi.org/10.1111/j.1365-2141.2009.07942.x] [PMID: 19821819]
[http://dx.doi.org/10.1038/sj.onc.1208246] [PMID: 15735759]
[http://dx.doi.org/10.1038/sj.bjc.6603143] [PMID: 16685275]
[http://dx.doi.org/10.3390/ijms19113536] [PMID: 30423986]
[PMID: 23749886]
[http://dx.doi.org/10.1053/hupa.2002.31292]] [PMID: 11957147]