Detection Method for Intravascular Invasion in Breast Cancer

This paper addresses the problem of peri- and intravascular invasion in invasive ductal carcinoma of the breast, not otherwise specified. A method for detecting intravascular invasion in breast cancer is proposed, which contributes to a more reliable assessment of the risk of tumor progression. This phenomenon, associated with hematogenous dissemination, including metastases to the brain nd bones, is frequently underrecognized in routine histopathological examination owing to the limitations of conventional light microscopy.

The aim of the study was a development of a pathological diagnostic method for detecting perivascular and intravascular tumor invasion in invasive breast carcinoma of no special type (IC NST).

Results. The method consists of two stages. In the first stage, histological diagnosis is performed using hematoxylin and eosin staining, after which the presence or absence of tumor cells in the lumen of blood vessels is determined. Then, in the second stage, an immunohistochemical study is carried out using antibodies to CD₃₁ — a marker of blood vessel endothelium — and AE1/AE3 antibodies to pan-cytokeratin, which stain blood vessel cells and tumor cells in different colors (double staining method). The presence of tumor cells in the lumen of blood vessels is then determined. If intravascular invasion is identified at either stage, there is a high probability of tumor progression. If the absence of intravascular invasion is established at both stages, this is assessed as a low probability of tumor progression. The detection of intravascular invasion correlated with an unfavorable prognosis and served as the basis for prescribing neoadjuvant chemotherapy and expanding the extent of lymph node dissection. Conclusion. The proposed approach allows for more accurate stratification of patients into risk groups, including those with negative lymph node status, and for optimization of treatment strategy.

1. Kushlinsky NE, Timofeev YuS, Gershtein ES, Soloviev YuN. Klinicheskie perspektivy issledovaniya komponentov sistemy [Clinical prospects of rank/rankl/opg system components study in primary and metastatic bone tumor]. Voprosy onkologii. 2014;60(4):414–422. (In Russian).

2. Mnikhovich MV, Shiripenko IA, Erofeeva LM, Bezuglova TV, Sidorova OA, et al. Lymphatic Architecture of Sappey Plexus and Lymphatic Metastasis of Breast Cancer. Voprosy onkologii. 2023;69(4):768–77. doi: 10.37469/0507-3758- 2023-69-4-768-777.

3. Mnikhovich MV, Bezuglova TV, Romanov AV, Shiripenko IA, Erofeeva LM, Tsymbalyuk VV, et al., inventors; Kursk State Medical University, assignee. Method for pedicting risk of tumor growth progression in breast cancer. Russian Federation Patent RU 2814748 C1. 2024 Mar 04.

4. Borriello L., Karagiannis GS, Duran CL, Coste A, Oktay MH, Entenberg D, et al. The role of the tumor microenvironment in tumor cell intravasation and dissemination. European journal of cell biology. 2020;99(6):151098. doi: 10.1016/j.ejcb.2020.151098

5. de Matos FR, Lima Ed, Queiroz LM, da Silveira EJ. Analysis of inflammatory infiltrate, perineural invasion, and risk score can indicate concurrent metastasis in squamous cell carcinoma of the tongue. J Oral Maxillofac Surg. 2012;70(7):1703-6. doi: 10.1016/j.joms.2011.08.023

6. Fujii T, Sutoh T, Morita H, Yajima R, Yamaguchi S, Tsutsumi S, et al. Vascular invasion, but not lymphatic invasion, of the primary tumor is a strong prognostic factor in patients with colorectal cancer. Anticancer Res. 2014;34(6):3147-51.

7. Hong SM, Jung D, Kiemen A, Gaida MM, Yoshizawa T, Braxton AM, et al. Threedimensional visualization of cleared human pancreas cancer reveals that sustained epithelialto-mesenchymal transition is not required for venous invasion. Mod Pathol. 2020;33(4):639- 647. doi: 10.1038/s41379-019-0409-3.

8. Jiang HY, Chen J, Xia CC, Cao LK, Duan T, Song B. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis. World J Gastroenterol. 2018;24(22):2348-2362. doi: 10.3748/wjg.v24.i22.2348.

9. Le Rhun E, Taillibert S, Zairi F, Kotecki N, Devos P, Mailliez A, et al. A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol. 2013;113(1):83-92. doi: 10.1007/s11060-013-1092-8.

10. Li P, Ling YH, Zhu CM, Hu WM, Zhang XK, Luo RZ, et al. Vascular invasion as an independent predictor of poor prognosis in nonmetastatic gastric cancer after curative resection. Int J Clin Exp Pathol. 2015;8(4):3910-8.

11. Meattini I, Andratschke N, Kirby AM, Sviri G, Offersen BV, Poortmans P, et al. Challenges in the treatment of breast cancer brain metastases: evidence, unresolved questions, and a practical algorithm. Clin Transl Oncol. 2020;22(10):1698- 1709. doi: 10.1007/s12094-020-02333-7.

12. Remo A, Sina S, Barbi S, Simeone I, Insolda J, Parcesepe P, et al. Wnt (canonical and non canonical) pathways in breast carcinoma with extensive vascular invasion and inflammatory breast carcinoma. Pathol Res Pract. 2021;219:153347. doi: 10.1016/j.prp.2021.153347

13. Vuong HG, Kondo T, Duong U, Pham TQ, Oishi N, Mochizuki K, et al. Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis. European journal of endocrinology. 2017;177(2):207–216. doi: 10.1530/EJE-17-0260