RELATIONSHIP BETWEEN PARAMETERS OF TUMOR NEOANGIOGENESIS AND LYMPHOGENOUS METASTASIS IN PATIENTS WITH RECTAL CANCER
https://doi.org/10.21294/1814-4861-2017-16-3-46-51
Abstract
Angiogenesis (neoangiogenesis) characterized by the formation of new blood vessels from pre-existing vessels is the main condition for the intensive growth of the primary tumor. This process is characterized by a sequence of events beginning with vasodilation, separation of pericytes from the vascular wall with subsequent proliferation of endotheliocytes and formation of vascular glomeruli surrounded by stromal cells. Evaluation of the density of microvessels, as well as «vascular kidneys» (clusters of endotheliocytes) is the most widely used method for quantifying intracellular angiogenesis. The purpose of the study was to analyze the expression characteristics of markers of neoangiogenesis (CD34 and VEGFR) in tumor tissue and to evaluate their relationship with the parameters of lymphogenous metastasis in colorectal cancer. Material and methods. Surgical specimens from 130 patients with ypT1–4N0–2M0 stage of rectal cancer, who were treated at the Thoracic and Abdominal Department of Tomsk Cancer Research Institute, were analyzed. The standard techniques for histological and immunohistochemical examinations were used. Diagnose was made according to WHO classification (2010). The study included only cases with rectal adenocarcinoma. Results. When studying the density of microvessels and «vascular budding» in a tumor tissue using an antibody to CD34, it turned out that the density of microvessels in the submucosal layer of the rectum was higher in cases with the presence of lymphogenous metastases than in cases without lymphogenous metastasis. The microvessel density determined by the antibody to VEGFR in the mucosa, submucosal and muscle layers, as well as in the serosa of the rectum did not differ between groups with the presence or absence of lymphogenous metastases. The density of «vascular kidneys» in all layers of the rectum wall was not associated with lymphogenous metastasis. Conclusion. The study showed that the expression of molecular-biological markers of neoangiogenesis in tumor tissue of patients with rectal adenocarcinoma was associated with the parameters of lymphogenous metastasis.
About the Authors
I. V. StepanovRussian Federation
pathologist
5, Kooperativny str., 634009-Tomsk
MD, PhD, Associate Professor of the Department of Pathological Anatomy
2, Moskovsky tract, 634050-Tomsk
SPIN-code: 5930-3160
S. R. Altybaev
Russian Federation
postgraduate, Department of Pathological Anatomy
2, Moskovsky tract, 634050-Tomsk
N. V. Krakhmal
Russian Federation
pathologist
5, Kooperativny str., 634009-Tomsk
MD, PhD, Department of Pathological Anatomy
2, Moskovsky tract, 634050-Tomsk
SPIN-code: 1543-6546
K. V. Rachkovsky
Russian Federation
postgraduate, Department of Pathological Anatomy
2, Moskovsky tract, 634050-Tomsk
SPIN-code: 6814-7094
D. A. Sorokin
Russian Federation
Postgraduate, Thoracic and Abdominal Department
5, Kooperativny str., 634009-Tomsk
S. G. Afanasyev
Russian Federation
MD, DSc, Professor, Chief Researcher, Thoracic and Abdominal Department
5, Kooperativny str., 634009-Tomsk
SPIN-code: 9206-3037
S. V. Vtorushin
Russian Federation
Leading Researcher
5, Kooperativny str., 634009-Tomsk
MD, DSc, Professor, Department of Pathological Anatomy
2, Moskovsky tract, 634050-Tomsk
SPIN-code: 2442-4720
M. V. Zavyalova
Russian Federation
MD, DSc, Professor, Senior Researcher, Department of Pathological Anatomy
5, Kooperativny str., 634009-Tomsk
Head of Pathological Anatomy Department
2, Moskovsky tract, 634050-Tomsk
References
1. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Intern J Cancer. 2015; 136 (5): E359–E386.
2. Afanasyev S.G., Dobrodeev A.Ju. Cytoreductive surgery (Should the primary tumor be removed? (What is the optimal cytoreduction?). Practical oncology. 2014; 15 (2): 93–100. [in Russian]
3. Goel S., Duda D.G., Xu L., Munn L.L., Boucher Y., Fukumura D., Jain R.K. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011 Jul; 91 (3): 1071–121. doi: 10.1152/ physrev.00038.2010.
4. Oklu R., Walker T.G., Wicky S., Hesketh R.J. Angiogenesis and current antiangiogenic strategies for the treatment of cancer. J Vasc Interv Radiol. 2010 Dec; 21 (12): 1791–805. doi: 10.1016/j.jvir.2010.08.009.
5. Marioni G., Staffiery A., Manzato E., Ralli G., Lionello M., Giacomelli L., Prosenikliev V., Marchese-Ragona R., Busnardo A., Bolzetta F., Blandamura S. A higher CD105-assessed microvessel density and vorse prognosis in elderly patients with laryngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2011 Feb; 137 (2): 175–80. doi: 10.1001/ archoto.2010.244.
6. Neri D., Bicknell R. The Discovery and Characterisation of Tumour Endothelial Markers. Vascular Disruptive Agents for the Treatment of Cancer. Springer New York, 2010; 31–48.
7. Seon B.K., Haba A., Matsuno F., Takahashi N., Tsujie M., She X., Harada N., Uneda S., Tsujie T., Toi H., Tsai H., Haruta Y. Endoglin-targeted cancer therapy. Curr Drug Deliv. 2011; 8 (1): 135–143.
8. Martins S.F., Reis R.M., Rodrigues A.M., Baltazar F., Longatto A. Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies. World J Clin Oncol. 2011; 2 (6): 272–80. doi: 10.5306/wjco.v2.i6.272.
9. ological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer. Mol Med Rep. 2016 Feb; 13 (2): 1551–7. doi: 10.3892/mmr.2015.4687
10. Arimoto A., Uehara K., Tsuzuki T., Aiba T., Ebata T., Nagino M. Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer. Int J Clin Oncol. 2015 Oct; 20 (5): 935–42. doi: 10.1007/s10147-015-0818-3.
11. Svagzdys S., Lesauskaite V., Pavalkis D., Nedzelskienė I., Pranys D., Tamelis A. Microvessel density as new prognostic marker after radiotherapy in rectal cancer. BMC Cancer. 2009; 9: 95. doi: 10.1186/1471- 2407-9-95.
12. Luengo-Gil G., González-Billalabeitia E., Chaves-Benito A., García Martínez E., García Garre E., Vicente V., Ayala de la Peña F. Effects of conventional neoadjuvant chemotherapy for breast cancer on tumor angiogenesis. Breast Cancer Res Treat. 2015 Jun; 151 (3): 577–87.
13. Ajili F., Kacem M., Tounsi H., Darouiche A., Enayfer E., Chebi M., Manai M., Boubaker S. Prognostic impact of angiogenesis in nonmuscle invasive bladder cancer as defined by microvessel density after immunohistochemical staining for CD34. Ultrastruct Pathol. 2012 Oct; 36 (5): 336–42.
Review
For citations:
Stepanov I.V., Altybaev S.R., Krakhmal N.V., Rachkovsky K.V., Sorokin D.A., Afanasyev S.G., Vtorushin S.V., Zavyalova M.V. RELATIONSHIP BETWEEN PARAMETERS OF TUMOR NEOANGIOGENESIS AND LYMPHOGENOUS METASTASIS IN PATIENTS WITH RECTAL CANCER. Siberian journal of oncology. 2017;16(3):46-51. (In Russ.) https://doi.org/10.21294/1814-4861-2017-16-3-46-51