Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Her-2 Protein in the Genesis of Cervical Carcinoma
DOI:
https://doi.org/10.3889/oamjms.2018.089Keywords:
Cervical carcinoma, Vascular endothelial growth factor, Her-2, Grade and stageAbstract
BACKGROUND: Angiogenesis plays a pivotal role in the progression of tumours through the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a chief factor responsible for inducing and regulating angiogenesis. Additionally, the human epidermal growth factor receptor family of receptors also plays an important role in the pathogenesis of tumours.
AIM: This study aimed to examine the association between VEGF and Her-2 protein expression and its correlation with clinic-pathological characteristics; in particular, prognosis.
METHODS: A total of 65 cases of cervical carcinoma and 10 samples of inflammatory lesions were evaluated for VEGF and Her-2 protein expression.
RESULTS: Expression of VEGF and Her-2 was detected in 63.07% and 43.07% in cervical carcinoma cases respectively whereas control cases did not show any expression. The difference in the expression pattern of both markers comparing cancer and control cases was statistically significant (p < 0.05). However, no significant difference in the expression pattern of VEGF protein was observed among the different grades and stages of tumours (p > 0.05). Comparing different grades of a tumour, expression of Her-2 was detected in 31.8% of well-differentiated tumours, 36.0 % in moderately differentiated tumours and 66.66 % in poorly differentiated cancers. The expression of Her-2 was increased in high-grade tumours, and the difference of expression level between tumour grades was statistically significant (p < 0.05). The expression level of Her-2 protein was not correlated with the stage of a tumour (p > 0.05).
CONCLUSION: The present study supports earlier findings that over-expression / up-regulation of VEGF and Her - 2 is linked with poor prognosis and may play a vital role in the development and progression of cervical cancer.Downloads
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Villa LL. Papillomaviruses and cervical cancer. Adv Cancer Res. 1997; 71:321-341. https://doi.org/10.1016/S0065-230X(08)60102-5
ZurHausen H. Papillomavirus infections - a major cause of human cancers. Biochim Biophys Acta. 19965; 1288:F55-F78.
Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12–19. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
Kajdaniuk D, Marek B, Borgiel-Marek H, Kos-Kudła B. Vascular endothelial growth factor (VEGF) - part 1: in physiology and pathophysiology. Endokrynol Pol. 2011; 62(5):444-55. PMid:22069106
Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003; 3:401–410. https://doi.org/10.1038/nrc1093 PMid:12778130
Kieser A, Weich HA, Brandner G et al. Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene. 1994; 9:963-969. PMid:8108142
Grugel S, Finkenzeller G, Weindel K et al. Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J BiolChem. 1995; 270:25915-25919. https://doi.org/10.1074/jbc.270.43.25915
Mukhopadhyay D, Tsiokas L, Sukhatme VP. Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res. 1995; 55:6161-6165. PMid:8521408
Warren RS, Yuan H, Matli MR et al. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem. 1996; 271:29483-29488. https://doi.org/10.1074/jbc.271.46.29483 PMid:8910616
Shariat SF, Youssef RF, Gupta A, Chade DC, Karakiewicz PI, Isbarn H, Jeldres C, Sagalowsky AI, Ashfaq R, Lotan Y. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol. 2010; 183(5):1744-50. https://doi.org/10.1016/j.juro.2010.01.018 PMid:20299037
Yarden Y, Sliwkowski MX. Untangling the ErbBsignalling network. Nat Rev Mol Cell Biol. 2001; 2:127–137. https://doi.org/10.1038/35052073 PMid:11252954
Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004; 4:361–370. https://doi.org/10.1038/nrc1360 PMid:15122207
Chong D, Cooke TG, Reeves JR et al. Quantitation of EGFR and c-erbB-2 expression in preinvasive compared to invasive breast cancers. ECCO 10 Conference, 12-16 September, 1999 (Abstr 792A) https://doi.org/10.1016/S0959-8049(99)81219-2
Rahmani AH, Babiker AY, Al Wanian WM, Elsiddig SA, Faragalla HE, Aly SM. Association of cytokeratin and vimentin protein in the genesis of transitional cell carcinoma of urinary bladder patients. Dis Markers. 2015; 2015:204759. https://doi.org/10.1155/2015/204759 PMid:26640315 PMCid:PMC4660019
Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990; 82:4-6. https://doi.org/10.1093/jnci/82.1.4 PMid:1688381
Folkman J. The vascularization of tumors. Sci Am. 1976; 234:58-73. https://doi.org/10.1038/scientificamerican0576-58 PMid:1273568
Folkman J. Tumor angiogenesis. In: Wells SA Jr, Sharp PA, editors. Accomplishments in Cancer Research. Pennsylvania: JB Lippincott Williams and Wilkins, 1998:32-44.
Donmez G, Sullu Y, Baris S, Yildiz L, Aydin O, Karagoz F, Kandemir B. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas. Pathol Res Pract. 2009; 205(12):854-7. https://doi.org/10.1016/j.prp.2009.07.015 PMid:19762163
Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med. 1998; 49:407-24. https://doi.org/10.1146/annurev.med.49.1.407 PMid:9509272
Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003; 6:653-660. https://doi.org/10.1038/nm0603-653 PMid:12778163
Risau W. Mechanisms of angiogenesis. Nature. 1997; 386:671-674. https://doi.org/10.1038/386671a0 PMid:9109485
Mandic A, UsajKnezevic S, KapiclIvkovic T. Tissue expression of VEGF in cervical intraepithelial neoplasia and cervical cancer. J BUON. 2014; 19(4):958-64. PMid:25536602
Fujiwaki R, Hata K, Iida K, Maede Y, Miyazaki K. Vascular endothelial growth factor expression in progression of cervical cancer: correlation with thymidine phosphorylase expression, angiogenesis, tumor cell proliferation, and apoptosis. Anticancer Res. 2000; 20(2B):1317-22. PMid:10810442
Al-Abbasi DS, Al-Janabi AA, Al-Toriahi KM, Jabor TA, YasseenAA. Expression of VEGF in urinary bladder transitional cell carcinoma in an Iraqi population subjected to depleted uranium: an immunohistochemical study. Appl Immunohistochem Mol Morphol. 2009; 17(4):307-11. https://doi.org/10.1097/PAI.0b013e3181941794 PMid:19151604
Rahmani A, Alzohairy M, Khadri H, Mandal AK, Rizvi MA. Expressional evaluation of vascular endothelial growth factor (VEGF) protein in urinary bladder carcinoma patients exposed to cigarette smoke. Int J Clin Exp Pathol. 2012; 5:195–202. PMid:22558473 PMCid:PMC3341674
Belfort-Mattos PN, Focchi GR, Speck NM, Taha NS, Carvalho CR, Ribalta JC. Immunohistochemical expression of granzyme B and vascular endothelial growth factor (VEGF) in normal uterine cervices and low and high grade squamous intraepithelial lesions. Eur J Gynaecol Oncol. 2010; 31:459–461. PMid:20882896
Goncharuk IV, Vorobjova LI, Lukyanova NY, Chekhun VF: Vascular endothelial growth factor expression in uterine cervical cancer: correlation with clinicopathologic characteristics and survival. Exp Oncol. 2009; 31(3):179-181. PMid:19783962
Schechter AL, Stern DF, Vaidyanathan L, et al. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984; 312:513–516. https://doi.org/10.1038/312513a0 PMid:6095109
Rubin I, Yarden Y. The basic biology of HER2. Ann Oncol. 2001; 12(Suppl 1):S3–S8. https://doi.org/10.1093/annonc/12.suppl_1.S3 PMid:11521719
KaptainS,Tan LK, Chen B. Her2 and breast cancer. Diagn Mol Path. 2001; 10:139–152. https://doi.org/10.1097/00019606-200109000-00001
Gravalos C, Jimeno A. Her2 in gastric cancer, a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008; 10:1093–1100. https://doi.org/10.1093/annonc/mdn169
Lee JS, Kim HS, Jung JJ, Lee MC, Park CS: Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression. Gynecol Oncol. 2002; 85:469-475. https://doi.org/10.1006/gyno.2002.6648
Gupta N, Singh S, Marwah N, Kumar S, Chabra S, Sen R. HER-2/neu expression in lesions of uterine cervix: is it reliable and consistent? Indian J Pathol Microbiol. 2009; 52(4):482-5. https://doi.org/10.4103/0377-4929.56127 PMid:19805951
Lakshmi S, Nair MB, Jayaprakash PG, Rajalekshmy TN, Nair MK, Pillai MR. c-erbB-2 oncoprotein and epidermal growth factor receptor in cervical lesions. Pathobiology. 1997; 65:163–168. https://doi.org/10.1159/000164118 PMid:9309783
Sarwade P, Patil S, Bindu R. Immunohistochemistry study for Her-2/neu expression in lesions of uterine cervix. Int J Cur Res Rev. 2016; 8:5-57.
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