Comparison of microvascular density in cervical carcinoma in relation to predictive pathohistological parameters

Aljoša Mandić; Tatjana  Ivković-Kapicl; Bojana  Gutić; Slobodan  Maričić; Nemanja Stevanović; Nenad Šolajić; Zoran Nikin; Tamara Maksimović; Tijana Stevanović

doi:10.2298/AOO240417009M

Aljoša Mandić Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Tatjana Ivković-Kapicl Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Bojana Gutić Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Slobodan Maričić Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Nemanja Stevanović Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Nenad Šolajić Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Zoran Nikin Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
Tamara Maksimović Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Tijana Stevanović University Clinical Center of Vojvodina, Obstetrics and Gynecology Clinic, Novi Sad, Serbia

DOI: https://doi.org/10.2298/AOO240417009M

Keywords: cervical cancer; microvascular density; angiogenesis; pathohistological parameters

Abstract

Objective: The occurrence, development, invasion, and metastasis of tumors are closely linked to angiogenesis, which is reflected by tumor microvessel density. The aim is to analyze microvascular density (MVD) in groups of patients with high grade squamos intraepithelial lesions (H-SIL), and cervical carcinoma, and to compare MVD in relation to the degree of tumor differentiation, size, presence of lymphovascular invasion and lymph node metastases. Materials and methods: The study was retrospective, conducted on histopathological samples of 109 patients who underwent hysterectomy with/without adnexectomy. Patients were divided into two groups depending on the histopathological results: group A - patients with H-SIL, and B with cervical cancer. The control group included surgically treated patiens with benign uterine diseases. Based on hematoxylin/eosine staining, representative sample was chosen for immunohistochemistry, and the analysis of CD34 antigen expression and measurement of MVD were done. Results: In order to subdivide groups according to the low (L) and high (H) MVD, in control, group A, and B, with mean MVDs 2.2; 9.85 and 17.19, respectively, a cut-off values were determined.

In the control group, LMVD 100% was measured. There were 7 (21.21%) in group A and 29 patients (63.04%) in group B with HMVD. A statistically significant difference was confirmed by comparing HMVD and LMVD in cervical cancer patients with lymph nodes metastasis (p<0.029). In the subgroup of patients with other worse pathohistological prognostic factors, a tumor size greater than 2 cm, depth of stromal invasion ˃10 mm, infiltration of “isthmus” of the uterus, a difference with no statistical significance was confirmed. Conclusion: Invasive cervical cancers are characterised by a significantly higher mean values of MVD compared to H-SIL. Significantly more often, HMVD is associated with the presence of lymph node metastases and histopathological parameters of poor prognosis.

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J for clinicians. 2021 May;71(3):209-49.

Mandic A, Usaj Knezevic S, Kapicl Ivkovic T. Tissue expression of VEGF in cervical intraepithelial neoplasia and cervical cancer. J Buon. 2014;19(4):958-964.

Hu X, Liu H, Ye M, Zhu X. Prognostic value of microvessel density in cervical cancer. Cancer Cell International. 2018 Dec;18(1):2-12. https://doi.org/10.1186/s12935-018-0647-3.

El Sabaa BM, Meleiss M, Zaki I. VEGF expression and microvascular density in relation to high-risk-HPV infection in cervical carcinoma–An immunohistochemical study. Alexandria J Medicine. 2012;48(1).

Yetkin-Arik B, Kastelein AW, Klaassen I, Jansen CH, Latul YP, Vittori M, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2021 Jan 1;1875(1):188446.

DiSaia PJ, Creasman WT, Mannell RS, McMeekin S, Mutch DG. Clinical gynecologic oncology e-book. Elsevier Health Sciences; 2017 Feb 4.who.int [homepage on the Internet]. Geneva: World Health Organisation. 2022 [update 2022; cited June 2022]. Available from: https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/.

Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1-8. doi: 10.1056/NEJM199101033240101.

Moriyama S, Kotera K, Khan KN, Sato F, So Y, Fujishita A, et al. Prognostic significance of tumor volume and microvessel density in squamous cell carcinoma of uterine cervix. Acta Medica Nagasakiensia. 2009;53(4):77-84.

Agnani B, Solanki R, Ansari M, Agnani S. Prognostic Significance of Microvessel Density as Assessed by anti CD34 Monoclonal Antibody in Invasive Ductal Carcinoma of Breast. Asian Pacific J Cancer Biology. 2020 Sep 15;5(3):75-9.

Liu D, Ding M.Predictive value of microvascular density for response to anlotinib in advanced NSCLC. Medicine. 2022 Jan 21;101(3):e28647 doi:10.1097/MD.0000000000028647.

Bais C, Mueller B, Brady MF, Mannel RS, Burger RA, Wei W, et al. NRG Oncology/Gynecologic Oncology Group. Tumor Microvessel Density as a Potential Predictive Marker for Bevacizumab Benefit: GOG-0218 Biomarker Analyses. J Natl Cancer Inst. 2017 Nov 1;109(11):djx066. doi: 10.1093/jnci/djx066.

Den Uil, SH, Van den Broek E, Coupé VMH , Vellinge TT, Delis-van Diemen PM, et al. Prognostic value of microvessel density in stage II and III colon cancer patients: a retrospective cohort study. BMC gastroenterol. 2019;19(146). doi:10.1186/s12876-019-063-4.

Cantu De León D, Lopez-Graniel C, Frias Mendivil M, Chanona Vilchis G, Gomez C, De La Garza Salazar J. Significance of microvascular density (MVD) in cervical cancer recurrence. Int J Gynecol Cancer. 2003 Nov-Dec;13(6):856-62. doi: 10.1136/ijgc-00009577-200311000-00018.

Wang M, Yuan B, Zhou ZH, Han WW. Clinicopathological characteristics and prognostic factors of cervical adenocarcinoma. Scientific Reports. 2021 Apr 5;11(1):1-8.

Aijaz M, Alam K, Maheshwari V. Evaluation of angiogenesis in cervical cancer using CD34 as a biomarker and its correlation with pathoanatomical features. Ann Cytology and Pathology. 2021 Jun 29;6(1):007-11.

Zhu J, Cao L, Wen H, Bi R, Wu X, Ke G. The clinical and prognostic implication of deep stromal invasion in cervical cancer patients undergoing radical hysterectomy. J Cancer. 2020;11(24):7368.