Vascular Endothelial Growth Factor (VEGF) expression and clinico-pathological characteristics of cervical cancer in the region of Casablanca-Settat

Metah El Khair Meryem, Elantri Said, Benhessou Mustapha, El Kerroumi Mohamed, Amine Abdessamad

Abstract


Background: The development of angiogenesis or novel blood vessels is essential to the tumors growth. Inducing and controlling angiogenesis is primarily the function of vascular endothelial growth factor (VEGF).

Methods: The expression of VEGF in tumor tissue from 327 cervical cancer cases treated at the Mohammed VI Center of Cancer Treatment Gynecological Obstetrics service of the Ibn Rochd Hospital (Casablanca) between 2013 and 2017 was investigated using an immunohistochemical technique.

Results: The average age was 50.93 ± 12.52 years. Squamous cell carcinoma accounted for 87.5% of all histological types. More than 76.4% of patients had cervical cancer that was in the middle or advanced stages when they first arrived. The cytoplasmic signal of VEGF was low in 93.3% of patients with high-grade intraepithelial lesions, higher in 87.5% of cases with stage IB2, and slightly lower in 71.4% of instances.

Conclusion: This study identified various issues and requirements of Moroccan women with cervical cancer. Our research will contribute to cervical cancer research in Morocco and aid in the development of novel methods. However, our findings indicate that VEGF is a critical biomarker that serves as a significant clinical predictor of the response of patients with cervix cancer to radiochemotherapy.

Keywords:

Angiogenesis, Cervix cancer, Vascular Endothelial Growth Factor, Radiochemotherapy


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References


Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians, (2018); 68(1): 7-30.

Bruni L, Albero G, Serrano B, Mena M, Collado JJ, Gómez D, Muñoz J, Bosch FX, de Sanjosé S. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Morocco. Summary Report 10 March 2023.

Tomao F, Papa A, Rossi L, Zaccarelli E, Caruso D, Zoratto F, et al. Angiogenesis and antiangiogenic agents in cervical cancer. OncoTargets and Therapy, (2014); 7: 2237-2248.

Minion LE, Tewari KS. Cervical cancer: state of the science—From angiogenesis blockade to checkpoint inhibition. Gynecologic Oncology, (2018); 148(3): 609-621.

Yu JQ, Zhou Q, Zhu H, Zheng FY, Chen ZW. Overexpression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and its correlation with angiogenesis. Asian Pacific Journal of Cancer Prevention, (2015); 16(6): 2277-2281.

Paduch R. The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cellular Oncology (Dordrecht), (2016); 39(5): 397-410.

Napoli Belfort-Mattos P, De Azevedo Focchi GR, Chamorro Lascasas Ribalta J, Megale De Lima T, Nogueira Carvalho CR, Kesselring Tso F, et al. Immunohistochemical expression of VEGF and podoplanin in uterine cervical squamous intraepithelial lesions. Disease Markers, (2016); 2016: 8293196.

Krill LS, Tewari S. Exploring the therapeutic rationale for angiogenesis blockade in cervical cancer. Clinical Therapeutics, (2015); 37(1): 9-19.

Willmott LJ, Monk BJ. Cervical cancer therapy: current, future and anti-angiogenesis targeted treatment. Expert Review of Anticancer Therapy, (2009); 9(7): 895-903.

Zhu P, Ou Y, Dong Y, Xu P, Yuan L. Expression of VEGF and HIF-1α in locally advanced cervical cancer: biomarkers for predicting radiochemotherapy response. OncoTargets and Therapy, (2016); 9: 3031-3037.

Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Critical Reviews in Biochemistry and Molecular Biology, (2000); 35(2): 71-103.

Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of Clinical Oncology, (2005); 23(5): 1011-1027.

Kanthou C, Dachs G, Lefley D, Steele A, Foxon C, Harris S, et al. Tumor cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics. PLoS One, (2014); 9(8): e104015.

Vosmik M, Laco J, Sirak I, Beranek M, Hovorkova E, Vosmikova H, et al. Prognostic significance of HPV status and biomarkers after chemoradiotherapy in cervical carcinoma. Pathology & Oncology Research, (2014); 20(1): 131-137.

Saijo Y, Furumoto H, Yoshida K, Nishimura M, Irahara M. Clinical significance of VEGF expression and microvessel density in invasive cervical cancer. Journal of Medical Investigation, (2015); 62(3-4): 154-160.

Fang L, Juiquan C. hTERT regulates VEGF expression via HPV-18 E7 in cervical cancer cells. Medical Oncology, (2015); 32(7): 199.

Abdulkarim B, Sabri S, Deutsch E, Chagraoui H, Maggiorella L, Eschwege F, et al. Cidofovir restores p53 function and enhances radiosensitivity in HPV-associated cancers. Oncogene, (2002); 21: 2334-2346.

Amine A, Vozenin-Brotons MC, Abdelhakim B, Violot D, Aubel C, Bourhis J. Cidofovir with radiation shows anti-angiogenic effect via E6 inhibition and TP53-dependent VEGF repression in HPV18+ cells. Radiation Research, (2006); 166: 600-610.

Perez CA, Grigsby PW, Chao KS, et al. Tumor size, irradiation dose, and long-term outcome in cervical carcinoma. International Journal of Radiation Oncology Biology Physics, (1998); 41: 307-317.

Fu Z, Chen D, Cheng H, Wang F. HIF-1α protects cervical carcinoma cells from radiation-induced apoptosis under hypoxia. Medical Science Monitor, (2015); 21: 318-325.

Moeller BJ, Dewhirst MW. HIF-1 and tumor radiosensitivity. British Journal of Cancer, (2006); 95(1): 1-5.

Meftah El Khair M, El Mzibri M, Ait Mhand R, Benider A, Benchekroun N, El Fahime EM, et al. Molecular detection and genotyping of HPV in cervical carcinoma in Moroccan women. Journal of Medical Virology, (2009); 81(4): 678-684.

Meftah El Khair M, Ennaji MM, El Kebbaj R, Ait Mhand R, Attaleb M, El Mzibri M. p53 codon 72 polymorphism and cervical cancer risk in Moroccan women. Medical Oncology, (2010); 27(3): 861-866.

Şahiner F, Kubar A, Gümral R, Ardıç M, Yiğit N, Şener K, et al. Efficiency of MY09/11 PCR in detecting multiple HPV infections. Diagnostic Microbiology and Infectious Disease, (2014); 80(1): 43-49.

Mwaka AD, Okello ES, Wabinga H, Walter FM. Symptomatic presentation with cervical cancer in Uganda. BMC Women’s Health, (2015); 15: 15.

Girianelli VR, Gamarra CJ, Azevedo e Silva G. Disparities in cervical and breast cancer mortality in Brazil. Revista de Saúde Pública, (2014); 48(3): 459-467.

Gien LT, Beauchemin MC, Thomas G. Adenocarcinoma: a unique cervical cancer. Gynecologic Oncology, (2010); 116(1): 140-146.

Berraho M, Bendahhou K, Obtel M, Zidouh A, Benider A, Errihani H, et al. Cervical cancer in Morocco: epidemiological profile. Asian Pacific Journal of Cancer Prevention, (2012); 13: 3153-3157.

Wang SS, Sherman ME, Hildesheim A, Lacey JV Jr, Devesa S. Cervical adenocarcinoma and squamous cell carcinoma trends in U.S. women, 1976–2000. Cancer, (2004); 100(5): 1035-1044.

Smith HO, Tiffany MF, Qualls CR, Key CR. Rising incidence of cervical adenocarcinoma: a 24-year population study. Gynecologic Oncology, (2000); 78(2): 97-105.

Karimi Zarchi M, Akhavan A, Fallahzadeh H, et al. Outcome of cervical cancer in Iranian women. Asian Pacific Journal of Cancer Prevention, (2010); 11(5): 1289-1291.

Kim HJ, Rhee WJ, Choi SH, Nam EJ, Kim SW, Kim S, et al. Adjuvant radiation therapy outcomes in early cervical cancer. Radiation Oncology Journal, (2015); 33(2): 126-133.

Wang J, Wang T, Yang YY, Chai YL, Shi F, Liu Z. Risk factors for early recurrence of cervical cancer. Molecular and Clinical Oncology, (2015); 3(2): 363-366.

Fagundes H, Perez CA, Grigsby PW, Lockett MA. Distant metastases after irradiation for cervical cancer. International Journal of Radiation Oncology Biology Physics, (1992); 24(2): 197-204.

Thomson CS, Forman D. Cancer survival in England: lessons from EUROCARE. British Journal of Cancer, (2009); 101(Suppl 2): S102-S109.

Vinh-Hung V, Bourgain C, Vlastos G, Cserni G, De Ridder M, Storme G, et al. Prognostic value of histopathology in cervical cancer: SEER study. BMC Cancer, (2007); 7: 164.

Peters WA, Liu PY, Barrett RJ, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. Journal of Clinical Oncology, (2023); 41(29): 4605-4612.

Depuydt CE, Boulet GAV, Horvath CAJ, Benoy IH, Vereecken AJ, Bogers JJ. MY09/11 PCR versus type-specific PCR for oncogenic HPV detection. Journal of Cellular and Molecular Medicine, (2007); 11(4): 881-891.

Lopez-Ocejo O, Viloria-Petit A, Bequet Romero M, Mukhopadhyay D, Rak J, Kerbel RS. HPV-16 E6 activates VEGF promoter independently of p53. Oncogene, (2000); 19(40): 4611-4620.

Zanotta N, Tornesello ML, Annunziata C, Stellato G, Buonaguro FM, Comar M. Immune mediators in young women with high-risk HPV. PLoS One, (2016); 11(3): e0151851.

Branca M, Ciotti M, Santini D, Bonito LD, Benedetto A, Giorgi C, et al. ERK/MAPK activation in cervical intraepithelial neoplasia lesions. American Journal of Clinical Pathology, (2004); 122(6): 902-911.

Ilahia NE, Bhattia A. Impact of HPV E5 on EGFR signaling. Microbial Pathogenesis, (2020); 139: 103923.

Van Trappen P, Steele D, Lowe DG, Baithun S, Beasley N, Thiele W, et al. VEGF-C, VEGF-D and VEGFR-3 expression in cervical carcinogenesis. Pathology, (2003); 35(4): 544-554.

Tjalma WA, Van Marck E, Weyler J, Dirix L, Vermeulen P, Goovaerts G, et al. Vascular endothelial growth factor expression and microvessel density in invasive cervical cancer. Journal of Obstetrics and Gynaecology Research, (2015); 41(1): 30-37.

Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Toi M, Matsumoto K, et al. Expression of vascular endothelial growth factor and its correlation with clinicopathologic factors in uterine cervical cancer. Gynecologic Oncology, (2009); 113(3): 476-485.

Vici P, Mariani L, Pizzuti L, et al. Emerging biological therapies for cervical carcinoma. Journal of Cancer, (2014); 5(2): 86-97.

Liu Y, Liu Z, Wang B, et al. Expression of VEGF and HIF-1α in locally advanced cervical cancer before and after preoperative radiochemotherapy. OncoTargets and Therapy, (2016); 9: 7403-7410.

Moeller BJ, Dewhirst MW. Hypoxia and radiosensitivity: role of hypoxia-inducible factor 1–mediated pathways in tumour radioresistance. Lancet Oncology, (2006); 7(6): 462-468.

Jayson GC, Kerbel R, Ellis LM, Harris AL. Anti-angiogenic therapy in oncology. Lancet, (2016); 388(10043): 518-529.

Braicu EI, Gasimli K, Richter R, Nassir M, Kummel S, Blohmer JU, et al. Serum VEGFA, TIMP2, MMP2, and MMP9 in radiochemotherapy monitoring. Anticancer Research, (2014); 34(1): 385-391.

Tewari KS, Sill MW, Long HJ III, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. New England Journal of Medicine, (2014); 370(8): 734-743.

Li H, Wu X, Cheng X, et al. Anti-angiogenic therapy in cervical cancer: current status and future perspectives. Cancer Treatment Reviews, (2023); 114: 102495.

Tian J, Cheng L, Kong E, Gu W, Jiang Y, Hao Q, et al. Linc00958/miR-185-5p/RSF-1 axis regulates cisplatin resistance and angiogenesis in cervical cancer. Reproductive Biology and Endocrinology, (2022); 20(1): 132.




DOI: https://doi.org/10.62940/als.v13i1.3484

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