Correlation of VEGF-C tissue expression and cervical lesion diameter on cervical cancer patients given neoadjuvant therapy

Heru Priyanto; Ambar Mudigdo; Andrijono Andrijono; Bhisma Murti

doi:10.15562/bmj.v8i1.1190

Correlation of VEGF-C tissue expression and cervical lesion diameter on cervical cancer patients given neoadjuvant therapy

Heru Priyanto ,

Ambar Mudigdo ,

Andrijono Andrijono ,

Bhisma Murti ,

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DOI: https://doi.org/10.15562/bmj.v8i1.1190 |
Published: 2019-04-01

Abstract

Background: Management of cervical cancer is still debated. The diameter of cervical lesions are predictors of lymph node metastases, lymphovascular invasion, survival rates and are related to cell hypoxia. VEGF-C plays a role in the process of angiogenesis and lymphangiogenesis which are important for metastasis.

Objective: To describe the correlation between VEGF-C tissue expression and the diameter of the cervical cancer lesion before and after being given neoadjuvant chemotherapy.

Methods: We conducted an observational study using consecutive sampling in the Obstetrics Gynecology and Anatomy Pathology Department of Dr. Moewardi Hospital, the teaching hospital of the Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia. A total of 30 tissue biopsies of IB2 and IIA2 cervical cancer patients before and after undergoing Paxus-Carboplatin chemotherapy were examined for immunohistological expression of VEGF-C. The diameter of the largest cervical lesions of each patient was recorded.

Result: The mean of the largest diameter of the cervical lesion prior to neoadjuvant chemotherapy was bigger than after neoadjuvant chemotherapy (5.62 vs. 3.50, p<0.001). A decrease in VEGF-C tissue expression was significantly related to the decrease in the diameter of the largest cervical lesion after neoadjuvant chemotherapy administration (p=0.008).

Conclusion: There is a significant negative correlation between VEGF-C tissue expression with the diameter of the cervical lesions given neoadjuvant chemotherapy.

References

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Eisenhauer EA, Therasse P, Bogaerts, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New Response Evaluation Criteria in Solid Tumours : Revised RECIST guideline (version 1.1). European Journal of Cancer. 2009;45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026.
Fuhrmannâ€Benzakein E, Ma MN, Rubbia-Brandt L, Mentha G, Ruefenacht D, Sappino AP, Pepper MS. Elevated levels of angiogenic cytokines in the plasma of cancer patients. International Journal of Cancer. 1999;85(1):40-5. DOI: 10.1002/(SICI)1097-0215(20000101)85:1<40::AID-IJC7>3.0.CO;2-L
Murti B. Desain dan ukuran sampel untuk penelitian kuantitatif dan kualitatif di bidang kesehatan. Yogyakarta: Gadjah Mada University Press; 2012.
Aziz MF. Faktor kliniko-patologik, molekul adhesi sel E-kadherin, katenin-A, dan enzim proteolitik matriks ekstraselular kathepsin-D sebagai prediktor metastasis kelenjar getah bening dan prognosis kanker serviks stadium awal. Jakarta: University of Indonesia; 2004.
Van Trappen PO, Ryan A, Carroll M, Lecoeur C, Goff L, Gyselman GL, Young BD, Lowe DG, Pepper MS, Shepherd JH, Jacobs IJ. A model for co-expression pattern analysis of genes implicated in angiogenesis and tumor cell invasion in cervical cancer. British Journal of Cancer. 2002; 27; 87(5): 537â€“544. DOI: 10.1038/sj.bjc.6600471.
Modarres M, Maghami FQ, Golvanaz M, Behtash N, Mousavi A, Khalili GR. Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IBâ€“IIB bulky cervical cancer and with tumor diameter greater than 4 cm. International Journal of Gynecological Cancer. 2005;15(3):483-8. DOI: 10.1111/j.1525-1438.2005.15312.x.
Chang TC, Lai CH, Hong JH, Hsueh S, Huang KG, Chou HH, Tseng CJ, Tsai CS, Chang JT, Lin CT, Chang HH, Chao PJ, Ng KK, Tang SG, Soong YK. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. Journal of Clinical Oncology. 2000;18(8): 1740-7. DOI: 10.1200/JCO.2000.18.8.1740.
Frumovitz M, Sood AK. Vascular endothelial growth factor (VEGF) pathway as a therapeutic target in gynecologic malignancies. Gynecologic Oncology. 2007; 104(3): 768â€“78. DOI: 10.1016/j.ygyno.2006.10.062
Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G. Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer research. 2000; 60(17):4693â€“6.
Andrijono. Kanker Serviks. 4th ed. Jakarta: Divisi Onkologi Departemen Obstetri-Ginekologi Fakultas Kedokteran Universitas Indonesia; 2012.
Franc M, Kachel-Flis A, Michalski B, Fila-Danilow A, Mazurek U, Michalski M, Michalska A, Kuczerawy I, dan Skrzypulec-Plinta V. Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB â€“ IIIB. Prz Menopauzalny. 2015; 14(2): 112-117. DOI: 10.5114/pm.2015.49397
Hassanein M, Callison JC, Callaway-Lane Cm, Aldrich MC, Grogan EL, Massion PP. The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila). 2012; 5(8): 992â€“1006. DOI: 10.1158/1940-6207.CAPR-11-0441
Grimaldi S, Terroir M, Caramella C. Advances in oncological treatment: Limitations of RECIST 1.1 criteria. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2018; 62(2):129-139. DOI: 10.23736/S1824-4785.17.03038-2

[1] Berek JS dan Hacker NF. 2015. Berek & Hacker's Gynecologic Oncology, 6th Edition. Wolters-Kluwer: Philadelphia.

[2] Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D.M, Forman D, Bray F. GLOBOCAN. 2012. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. World Health Organization.

[3] Eisenhauer EA, Therasse P, Bogaerts, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New Response Evaluation Criteria in Solid Tumours : Revised RECIST guideline (version 1.1). European Journal of Cancer. 2009;45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026.

[4] Fuhrmannâ€Benzakein E, Ma MN, Rubbia-Brandt L, Mentha G, Ruefenacht D, Sappino AP, Pepper MS. Elevated levels of angiogenic cytokines in the plasma of cancer patients. International Journal of Cancer. 1999;85(1):40-5. DOI: 10.1002/(SICI)1097-0215(20000101)85:1<40::AID-IJC7>3.0.CO;2-L

[5] Murti B. Desain dan ukuran sampel untuk penelitian kuantitatif dan kualitatif di bidang kesehatan. Yogyakarta: Gadjah Mada University Press; 2012.

[6] Aziz MF. Faktor kliniko-patologik, molekul adhesi sel E-kadherin, katenin-A, dan enzim proteolitik matriks ekstraselular kathepsin-D sebagai prediktor metastasis kelenjar getah bening dan prognosis kanker serviks stadium awal. Jakarta: University of Indonesia; 2004.

[7] Van Trappen PO, Ryan A, Carroll M, Lecoeur C, Goff L, Gyselman GL, Young BD, Lowe DG, Pepper MS, Shepherd JH, Jacobs IJ. A model for co-expression pattern analysis of genes implicated in angiogenesis and tumor cell invasion in cervical cancer. British Journal of Cancer. 2002; 27; 87(5): 537â€“544. DOI: 10.1038/sj.bjc.6600471.

[8] Modarres M, Maghami FQ, Golvanaz M, Behtash N, Mousavi A, Khalili GR. Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IBâ€“IIB bulky cervical cancer and with tumor diameter greater than 4 cm. International Journal of Gynecological Cancer. 2005;15(3):483-8. DOI: 10.1111/j.1525-1438.2005.15312.x.

[9] Chang TC, Lai CH, Hong JH, Hsueh S, Huang KG, Chou HH, Tseng CJ, Tsai CS, Chang JT, Lin CT, Chang HH, Chao PJ, Ng KK, Tang SG, Soong YK. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. Journal of Clinical Oncology. 2000;18(8): 1740-7. DOI: 10.1200/JCO.2000.18.8.1740.

[10] Frumovitz M, Sood AK. Vascular endothelial growth factor (VEGF) pathway as a therapeutic target in gynecologic malignancies. Gynecologic Oncology. 2007; 104(3): 768â€“78. DOI: 10.1016/j.ygyno.2006.10.062

[11] Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G. Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer research. 2000; 60(17):4693â€“6.

[12] Andrijono. Kanker Serviks. 4th ed. Jakarta: Divisi Onkologi Departemen Obstetri-Ginekologi Fakultas Kedokteran Universitas Indonesia; 2012.

[13] Franc M, Kachel-Flis A, Michalski B, Fila-Danilow A, Mazurek U, Michalski M, Michalska A, Kuczerawy I, dan Skrzypulec-Plinta V. Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB â€“ IIIB. Prz Menopauzalny. 2015; 14(2): 112-117. DOI: 10.5114/pm.2015.49397

[14] Hassanein M, Callison JC, Callaway-Lane Cm, Aldrich MC, Grogan EL, Massion PP. The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila). 2012; 5(8): 992â€“1006. DOI: 10.1158/1940-6207.CAPR-11-0441

[15] Grimaldi S, Terroir M, Caramella C. Advances in oncological treatment: Limitations of RECIST 1.1 criteria. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2018; 62(2):129-139. DOI: 10.23736/S1824-4785.17.03038-2

Correlation of VEGF-C tissue expression and cervical lesion diameter on cervical cancer patients given neoadjuvant therapy

Abstract

References

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