MORPHOLOGICAL FEATURES OF TUMOR ANGIOGENESIS IN INVASIVE DUCTAL BREAST CANCER

Keywords: microvessels, breast carcinoma, immunohistochemistry, prognosis, angiogenesis

Abstract

Personalized treatment of patients with invasive ductal breast cancer is one of the most pressing issues in modern oncology. Today, information on the human genome and molecular markers is used to targeted therapy and optimize treatment strategies. One of the molecular markers is abnormal tumor angiogenesis. PECAM-1, or CD31, may be a marker of this process. The aim of the study was to comprehensively assess the morphological features and clinical significance of different types of tumors microvessels in invasive ductal breast cancer. CD31 expression was assessed by positive vascular endothelial staining. Using antibodies to CD31 (Ab-1, JC70A, Thermo scientific), we investigated 86 cases of invasive ductal breast cancer. In histological specimens stained with antibodies to CD31, the density of microvessels and areas with strong vascularization, the presence of dilated and atypical dilated capillaries in the intratumoral and peritumoral stroma, the presence of structures with local endothelial lining were assessed. The number of dilated and atypical dilated capillaries, as well as structures with partial endothelial lining was estimated by the semi-quantitative method. According to the results of our study, we showed some differences in the severity of vascular density of the tumor in patients with invasive ductal breast cancer. No differences in microvascular density were found depending on the age of the patients, T and N stages. At the same time, higher values of microvascular density in the intratumoral stroma were noted at G3 degree of differentiation, in triple-negative breast cancer and at HER2/neu positive. The most significant from the prognostic point of view were the number of atypical dilated vessels and structures with local endothelial lining, as well as the presence of characteristic porous structures in loose softly fibrous unformed connective tissue of the peritumoral stroma. Angiogenesis, morphology of tumor vessels is important for prognostic value and this marker can be used to predict the course of invasive ductal breast cancer.

References

1. WHO, 2021 Breast cancer now most common form of cancer: WHO taking action. Available from: https://www.who. int/news/item/03-02-2021-breast-cancer-now-most-common-form-ofcancer-who-taking-action.
2. Parkin DM, Bray F, Ferlay J, Pisani P. (2005). Global cancer statistics, 2002. CA Cancer J Clin. Mar-Apr;55(2):74-108. doi: 10.3322/canjclin.55.2.74. PMID: 15761078.
3. Breast Cancer. WHO, 2021. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
4. Bulletin of national cancer registry of Ukraine (English). (2020). Cancer in Ukraine, 2018-2019. Ukrainian cancer registry statistics, Vol.21 “Cancer in Ukraine”, 2018–2019.
5. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0. PMID: 15894097.
6. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn HJ; (2007). 10th St. Gallen conference. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. Jul;18(7):1133-44. doi: 10.1093/annonc/mdm271. Erratum in: Ann Oncol. 2007 Nov;18(11):1917. PMID: 17675394.
7. Folkman J. (1976). The vascularization of tumors. Sci Am.J 234 (5): 58-64, 70-3.
8. Shen Y., Quan J., Wang M. et al. (2017). Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer. Oncotarget. 8 (34): 56408-56416. doi: 10.18632/oncotarget.16919.
9. Liu H., Jiang Y., Dai Q. et al. (2014). Peripheral enhancement of breast cancers on contrastenhanced ultrasound: correlation with microvessel density and vascular endothelial growth factor expression. Ultrasound Med Biol. 40 (2): 293-9. doi: 10.1016/j.ultrasmedbio.2013.10.004.
10. Şener E., Şipal S., Gündoğdu C. (2016). Comparison of microvessel density with prognostic factors in invasive ductal carcinomas of the breast. Turk Patoloji Dergisi. 32(3): 164–70. doi:10.5146/tjpath.2016.01366.
11. Kraby M.R., Opdahl S., Akslen L.A. et al. (2017). Quantifying tumour vascularity in nonluminal breast cancers. J Clin Pathol. 70 (9): 766–774. doi: 10.1136/jclinpath-2016-204208.
12. Han Z., Chen Z., Zheng R. et al. (2015). Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relationship to angiogenesis. World J Surg Oncol. 13, Article ID 56. doi:10.1186/s12957-015-0486-9.
13. Shrivastav S., Bal A., Singh G., Joshi K. (2016). Tumor angiogenesis in breast cancer: pericytes and maturation does not correlate with lymph node metastasis and molecular subtypes. Clin Breast Cancer. 16 (2):131–138.
14. Zhang S., Zhang D., Gong M. et al. (2017). High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer. BMC Cancer. 17: 335. doi: 10.1186/s12885-017-3338-x.
15. Mohammed Z.M., McMillan D.C., Edwards J. et al. (2013). The relationship between lymphovascular invasion and angiogenesis, hormone receptors, cell proliferation and survival in patients with primary operable invasive ductal breast cancer. BMC Clin Pathol. 13 (1): 31. doi: 10.1186/1472-6890-13-31.
16. Chuangsuwanich T., Pongpruttipan T., O-Charoenrat P. et al. (2014). Clinicopathologic features of breast carcinomas classified by biomarkers and correlation with microvessel density and VEGF expression: a study from Thailand. Asian Pac J Cancer Prev. 15 (3): 1187-1192.
17. Fukumura D., Duda D.G., Munn L.L. et al. (2010). Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation. 17 (3): 206–25.
18. Birau A., Ceausu R.A., Cimpean A.M. et al. (2012). Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma. Oncol Lett. 4 (6): 1183–1186.
19. Nagy J.A., Dvorak H.F. (2012). Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets. Clin Exp Metastasis. 29(7): 657-62. doi: 10.1007/s10585-012-9500-6.
20. Qian C.N., Tan M.H., Yang J.P. et al. (2016). Revisiting tumor angiogenesis: vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation. Chin J Cancer. 35: 10. doi: 10.1186/s40880-015-0070-2.
21. WHO Classification of Tumors Editorial Board, ed. WHO classification of tumors. 5th edition. Breast tumors. Lyon: International Agency for Research on Cancer; 2019. PMID: 32056259. doi: 10.1111/his.14091
22. Elston CW, Ellis IO. (1991). Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 19: 403-10. PMID: 1757079. doi: 10.1111/j.1365-2559.1991.tb00229.x
23. Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al; (2015). Panel Members. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. Aug;26(8):1533-46. PMID: 25939896. PMCID: PMC4511219. doi: 10.1093/annonc/mdv221
24. Allison KH, Hammond MEH, Dowsett M. et al. (2020). Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Arch Pathol Lab Med. May;144(5):545-563. doi: 10.5858/arpa.2019-0904-SA. Epub 2020 Jan 13. PMID: 31928354
25. Bosari S, Lee AK, DeLellis RA, Wiley BD, Heatley GJ, Silverman ML. (1992). Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol; 23:755–61.
26. Nico B, Benagiano V, Mangieri D, Maruotti N, Vacca A, Ribatti D. (2008). Evaluation of microvascular density in tumors: pro and contra. Histol Histopathol.; 23:601-607.
27. Spirina L.V., Kondakova I.V., Usynin E.A., Vintizenko S.I. (2008). Regulyaciya angiogeneza pri zlokachestvennyh opuholyah pochki i mochevogo puzyrya. Sibirskij onkologicheskij zhurnal.; 4:66-70.
28. Stepanova E.V., Lichinicer M.R., Vartanyan A.A. (2006). Vaskulogennaya mimikriya pri zlokachestvennyh novoobrazovaniyah. Molekulyarnaya medicina; 1:23-30.
29. Gershtejn E.S., Kushlinskij D.N., Degtyar’ V.G. (2013). Faktor rosta endoteliya sosudov kak osnovnoj regulyator angiogeneza i klinicheski znachimyj pokazatel’ pri razlichnyh zlokachestvennyh novoobrazovaniyah. Tekhnologii zhivyh sistem.; 10:18-33.
30. Qiao L, Liang N, Zhang J et al. (2015). Advanced research on vasculogenic mimicry in cancer. J Cell Mol Med.; 19:315-326. doi:10.1111/jcmm.12496.

Abstract views: 186
PDF Downloads: 136
Published
2022-04-28
How to Cite
Volos, L., & Dudash, A. (2022). MORPHOLOGICAL FEATURES OF TUMOR ANGIOGENESIS IN INVASIVE DUCTAL BREAST CANCER. Scientific Journal of Polonia University, 50(1), 269-280. https://doi.org/10.23856/5032
Section
HEALTH, ENVIRONMENT, DEVELOPMENT