Expression and Significance of Vascular Endothelial Growth  Factor Receptors 2 and 3 in Endometrial Carcinoma

Nadia Y. Ibrahiem

doi:10.54172/mjsc.1375

Authors

Nadia Y. Ibrahiem Obstetrics and Gynecology, Faculty of Medicine, Omar Al Mukhtar University, Libya.

DOI:

https://doi.org/10.54172/mjsc.1375

Keywords:

Endometrial carcinoma, VEGF receptor, VEGF receptors2-3

Abstract

The aim of this work is to evaluate the expression and significance of Vascular Endothelial (VEGFR2,3) in endometrim. The study was applied to 70 females selected from El-Shatby University Hospital. Group I: 35 patients with dysfunctional uterine bleeding. Group II: 35 patients diagnosed with endometrial carcinoma. In the present work, VEGFRs 2 and 3 expression was detected by quantitative real-time PCR. The results revealed that: regarding relative VEGFR gene quantitation, there were no significant differences in the rates of VEGFR 2 and 3 expression between controls and cases. Regarding VEGFR 2 and 3 with type I & II, low and high histological grade, early and late stage, and lymphovascular invasion of endometrial cancer cases, there was no statistically significant relation. In this particular study, it was concluded that the expression levels of VEGFR2 and VEGFR3 do not exhibit any significant increase in endometrial cancers compared to dysfunctional uterine bleeding. Furthermore, we have observed that there exists no discernible correlation between VEGFR2 and VEGFR3 with regard to the histological type, grade, stage, or lymphovascular invasion of the endometrial cancer case.

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References

Amant, F., Moerman, P., Neven, P., Timmerman, D., Van Limbergen, E., & Vergote, I. (2005). Endometrial cancer. The Lancet, 366(9484), 491-505.

Beddy, P., O'Neill, A. C., Yamamoto, A. K., Addley, H. C., Reinhold, C., & Sala, E. (2012). FIGO staging system for endometrial cancer: added benefits of MR imaging. Radiographics, 32(1), 241-254.

Berchuck, A., Soisson, A., Olt, G. J., Soper, J. T., Clarke-Pearson, D. L., Bast Jr, R. C., & McCarty Jr, K. (1989). Epidermal growth factor receptor expression in normal and malignant endometrium. American journal of obstetrics and gynecology, 161(5), 1247-1252.

Boocock, C. A., Charnock-Jones, D. S., Sharkey, A. M., McLaren, J., Barker, P. J., Wright, K. A., Twentyman, P. R., & Smith, S. K. (1995). Expression of vascular endothelial growt factor and its receptors fit and KDR in ovarian carcinoma. JNCI: Journal of the National Cancer Institute, 87(7), 506-516.

Brinton, L. (1992). Epidemiology of gynecologic cancers. Principles and practice of gynecologic oncology, 3-26.

Brown, L. F., Berse, B., Jackman, R. W., Tognazzi, K., Manseau, E. J., Senger, D. R., & Dvorak, H. F. (1993). Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer research, 53(19), 4727-4735.

Brys, M., Semczuk, A., Rechberger, T., & Krajewska, W. M. (2007). Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium. Oncology Reports, 18(1), 261-265.

Chan, J. K., Urban, R., Cheung, M. K., Shin, J. Y., Husain, A., Teng, N. N., Berek, J. S., Walker, J. L., Kapp, D. S., & Osann, K. (2007). Lymphadenectomy in endometrioid uterine cancer staging: how many lymph nodes are enough? A study of 11,443 patients. Cancer, 109(12), 2454-2460.

Chin, K., Kurashima, Y., Ogura, T., Tajiri, H., Yoshida, S., & Esumi, H. (1997). Induction of vascular endothelial growth factor by nitric oxide in human glioblastoma and hepatocellular carcinoma cells. Oncogene, 15(4), 437-442.

Donoghue, J. F., Lederman, F. L., Susil, B. J., & Rogers, P. A. (2007). Lymphangiogensis of normal endometrium and endometrial adenocarcinoma. Human Reproduction, 22(6), 1705-1713.

Elwood, J. M., Cole, P., Rothman, K. J., & Kaplan, S. D. (1977). Epidemiology of endometrial cancer. Journal of the National Cancer Institute, 59(4), 1055-1060.

Erdem, O., Erdem, M., Erdem, A., Memis, L., & Akyol, G. (2007). Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma. International Journal of Gynecologic Cancer, 17(6).

Ferrara, N., Houck, K., Jakeman, L., & Leung, D. W. (1992). Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocrine reviews, 13(1), 18-32.

Folkman, J. (1990). What is the evidence that tumors are angiogenesis dependent? (Vol. 82, pp. 4-7): Citeseer.

Folkman, J. (1995). Clinical applications of research on angiogenesis. New England Journal of Medicine, 333(26), 1757-1763.

Giatromanolaki, A., Sivridis, E., Brekken, R., Thorpe, P. E., Anastasiadis, P., Gatter, K. C., Harris, A. L., & Koukourakis, M. I. (2001). The angiogenic “vascular endothelial growth factor/flk‐1 (KDR) receptor” pathway in patients with endometrial carcinoma: prognostic and therapeutic implications. Cancer: Interdisciplinary International Journal of the American Cancer Society, 92(10), 2569-2577.

Guidi, A. J., Abu-Jawdeh, G., Berse, B., Jackman, R. W., Tognazzi, K., Dvorak, H. F., & Brown, L. F. (1995). Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. JNCI: Journal of the National Cancer Institute, 87(16), 1237-1245.

Hanahan, D., & Folkman, J. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. cell, 86(3), 353-364.

Hill, H. A., Eley, J. W., Harlan, L. C., Greenberg, R. S., Barrett II, R. J., & Chen, V. W. (1996). Racial differences in endometrial cancer survival: the black/white cancer survival study. Obstetrics & Gynecology, 88(6), 919-926.

Holland, J. F. (2010). Holland-Frei cancer medicine 8 (Vol. 8). PMPH-USA.

Jeltsch, M., Kaipainen, A., Joukov, V., Meng, X., Lakso, M., Rauvala, H., Swartz, M., Fukumura, D., Jain, R. K., & Alitalo, K. (1997). Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science, 276(5317), 1423-1425.

Kieser, A., Weich, H. A., Brandner, G., Marmé, D., & Kolch, W. (1994). Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene, 9(3), 963-970.

Kim, J. Y., BAE, B. N., Kwon, J. E., KIM, H. J., & Park, K. (2011). Prognostic significance of epidermal growth factor receptor and vascular endothelial growth factor receptor in colorectal adenocarcinoma. Apmis, 119(7), 449-459.

Lozano-Leon, A., Perez-Quintela, B. V., Iglesias-García, J., Lariño-Noia, J., Varo, E., Forteza, J., & Domínguez-Muñoz, J. E. (2011). Ductal adenocarcinoma of the pancreas: Expression of growth factor receptors, oncogenes and suppressor genes, and their relationship to pathological features, staging and survival. Oncology Letters, 2(1), 161-166.

McCluggage, G., Hirschowitz, L., Ganesan, R., Kehoe, S., & Nordin, A. (2010). Which staging system to use for gynaecological cancers: a survey with recommendations for practice in the UK. Journal of clinical pathology, 63(9), 768-770.

McDonald, T. W., Annegers, J. F., O'Fallon, W. M., Dockerty, M. B., Malkasian Jr, G. D., & Kurland, L. T. (1977). Exogenous estrogen and endometrial carcinoma: case-control and incidence study. American journal of obstetrics and gynecology, 127(6), 572-580.

McNamara, D., Harmey, J., Walsh, T., Redmond, H., & Bouchier‐Hayes, D. (1998). Significance of angiogenesis in cancer therapy. British journal of surgery, 85(8), 1044-1055.

Neufeld, G., Cohen, T., Gengrinovitch, S., & Poltorak, Z. (1999). Vascular endothelial growth factor (VEGF) and its receptors. The FASEB journal, 13(1), 9-22.

Papanikolaou, A., Kalogiannidis, I., Goutzioulis, M., Misailidou, D., Makedos, A., Vergote, I., & Makedos, G. (2006). Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer. Archives of Gynecology and Obstetrics, 274, 91-96.

Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O., & Alitalo, K. (1994). Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. Journal of biological chemistry, 269(9), 6271-6274.

Plataniotis, G., & Castiglione, M. (2010). Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21, v41-v45.

Poon, R. T.-P., Fan, S.-T., & Wong, J. (2001). Clinical implications of circulating angiogenic factors in cancer patients. Journal of Clinical Oncology, 19(4), 1207-1225.

Rak, J., Mitsuhashi, Y., Bayko, L., Filmus, J., Shirasawa, S., Sasazuki, T., et al., & Kerbel, R. (1995). Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer research, 55(20), 4575-4580.

Shweiki, D., Itin, A., Soffer, D., & Keshet, E. (1992). Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature, 359(6398), 843-845.

Smith, S. (1998). Angiogenesis, vascular endothelial growth factor and the endometrium. Human Reproduction Update, 4(5), 509-519.

Takahashi, Y., Bucana, C. D., Liu, W., Yoneda, J., Kitadai, Y., Cleary, K. R., & Ellis, L. M. (1996). Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. JNCI: Journal of the National Cancer Institute, 88(16), 1146-1151.

Thompson, W. D., Li, W. W., & Maragoudakis, M. (1999). The clinical manipulation of angiogenesis: pathology, side‐effects, surprises, and opportunities with novel human therapies. The Journal of pathology, 187(5), 503-510.

van't Veer, M. B., Brooijmans, A. M., Langerak, A. W., Verhaaf, B., Goudswaard, C. S., Graveland, W. J., van Lom, K., & Valk, P. (2006). The predictive value of lipoprotein lipase for survival in chronic lymphocytic leukemia. Haematologica, 91(1), 56-63.

Wang, J., Taylor, A., Showeil, R., Trivedi, P., Horimoto, Y., Bagwan, I., Ewington, L., Lam, E. W.-F., & El-Bahrawy, M. A. (2014). Expression profiling and significance of VEGF-A, VEGFR2, VEGFR3 and related proteins in endometrial carcinoma. Cytokine, 68(2), 94-100.

Yokoyama, Y., Sato, S., Futagami, M., Fukushi, Y., Sakamoto, T., Umemoto, M., & Saito, Y. (2000). Prognostic significance of vascular endothelial growth factor and its receptors in endometrial carcinoma. Gynecologic oncology, 77(3), 413-418.