Immunohistochemical expression of vascular endothelial growth factor-C in renal cell carcinoma subtypes
Ekspresi imunohistokimia faktor pertumbuhan endotel vaskular-C pada subtipe karsinoma sel ginjal
DOI:
https://doi.org/10.21070/ijhsm.v2i1.180Keywords:
Renal Cell Carcinoma, Vascular Endothelial Growth Factor-C, Clear Cell Carcinoma, Tumor Grade, Lymphovascular InvasionAbstract
Background: Vascular Endothelial Growth Factor-C is a glycoprotein encoded by the Vascular Endothelial Growth Factor-C gene, initially produced as an inactive precursor and activated through proteolytic processing. It belongs to the vascular endothelial growth factor family and plays a crucial role in angiogenesis (blood vessel formation) and lymphangiogenesis. Objectives of the study: To evaluate the immunohistochemical expression of Vascular Endothelial Growth Factor-C in renal cell carcinoma subtypes. To assess its association with some clinicopathological parameters. Methods: In this prospective and retrospective case series study, fifty cases of surgically excised kidney biopsies were included. The blocks of the cases were collected from Al-Jumhory teaching hospital and some private laboratories in Mosul city in a period from October 2023 to July 2024. Section slides from the blocks were stained by Vascular Endothelial Growth Factor-C. Interpretation of the slides and statistical analysis has been done. Results: The age of 50 renal cell carcinoma cases ranged from 21 to 77 years (mean± standard deviation= 55.6±13.5) with 56% of them ≥ 55 years, male to female ratio 2:3, 78% of cases were of clear cell renal cell carcinoma, regarding tumor grading 44% grade II, 34% with positive lymphovascular invasion, 48% were tumor stage T1. Among the fifty cases, 56% were with high level of expression of VEGF-C with 59% of them < 55 years old, 63% males, 56% were of clear cell renal cell carcinoma, 82.4% of them with positive lymphovascular invasion show high expression of VEGF-C. Conclusion: High VEGF-C expression was predominantly observed in cases with higher tumor grades (III and IV), also there is a high expression with advanced stages (T3 and T4), and lymphovascular invasion, suggesting that VEGF-C may serve as an important parameter for more aggressive and invasive forms of RCC.
Highlight :
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High VEGF-C expression significantly correlates with advanced tumor grade (III–IV) and stage (T3–T4), indicating aggressive cancer behavior.
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VEGF-C shows strong association with lymphovascular invasion, suggesting its role in tumor dissemination and poor prognosis.
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VEGF-C expression may serve as a potential biomarker for identifying invasive renal cell carcinoma and guiding targeted therapy.
Keywords : Renal Cell Carcinoma, Vascular Endothelial Growth Factor-C, Clear Cell Carcinoma, Tumor Grade, Lymphovascular Invasion
References
[1] J. S. Robson, D. L. Vay, and G. A. G. Mitchell, "Renal System," Encyclopedia Britannica, vol. 1, 2023.
[2] M. Jeltsch et al., "CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease With Thrombospondin Motifs-3-Mediated Vascular Endothelial Growth Factor-C Activation," Circulation, vol. 129, no. 19, pp. 1962–1971, May 2014.
[3] M. Voss et al., "The Lymphatic System and Its Specific Growth Factor Vascular Endothelial Growth Factor C in Kidney Tissue and in Renal Cell Carcinoma," BJU International, vol. 104, no. 1, pp. 94–99, Jul. 2009.
[4] L. Shi et al., "Expression of Vascular Endothelial Growth Factor C in Renal Cell Carcinoma and Its Correlation With Pathological Parameters and Prognosis," Translational Andrology and Urology, vol. 9, no. 4, pp. 1670–1677, Aug. 2020.
[5] K. Rauniyar, S. K. Jha, and M. Jeltsch, "Biology of Vascular Endothelial Growth Factor C in the Morphogenesis of Lymphatic Vessels," Frontiers in Bioengineering and Biotechnology, vol. 6, article 7, Feb. 2018, doi: 10.3389/fbioe.2018.00007.
[6] J. Zhao, S. Chen, W. Li, and Y. Zhang, "Immunohistochemical Expression of VEGF-C in Renal Cell Carcinoma and Its Association With Lymph Node Metastasis: A Chinese Population Study," Chinese Journal of Urology, vol. 38, no. 4, pp. 310–317, 2017.
[7] A. A. Moselhy, D. R. Al-Sharaky, M. M. Dawoud, and M. A. Kandil, "The Study of Immunohistochemical Expression of Vascular Endothelial Growth Factor in Renal-Cell Carcinoma," Menoufia Medical Journal, vol. 35, no. 2, pp. 578–587, 2022.
[8] S. Bierer et al., "Lymphangiogenesis in Kidney Cancer: Expression of VEGF-C, VEGF-D and VEGFR-3 in Clear Cell and Papillary Renal Cell Carcinoma," Oncology Reports, vol. 20, no. 4, pp. 721–725, Oct. 2008.
[9] J. B. Rubin et al., "Sex Differences in Cancer Mechanisms," Biology of Sex Differences, vol. 11, pp. 1–29, Dec. 2020.
[10] M. Gerlinger et al., "Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing," New England Journal of Medicine, vol. 366, no. 10, pp. 883–892, Mar. 2012.
[11] S. Karaman and M. Detmar, "Mechanisms of Lymphatic Metastasis," The Journal of Clinical Investigation, vol. 124, no. 3, pp. 922–928, Mar. 2014.
[12] Z. Guillaume et al., "Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies," Cancers, vol. 14, no. 24, article 6167, Dec. 2022.
[13] B. Escudier et al., "Renal Cell Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up," Annals of Oncology, vol. 30, no. 5, pp. 706–720, May 2019.
[14] L. Choueiri and T. Powles, "Renal Cell Carcinoma: Recent Advances and Emerging Therapies," Nature Reviews Clinical Oncology, vol. 18, no. 8, pp. 479–490, Aug. 2021, doi: 10.1038/s41571-021-00501-1.
[15] M. Li et al., "Prognostic Value of VEGF-C Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis," Frontiers in Oncology, vol. 12, article 812015, Mar. 2022, doi: 10.3389/fonc.2022.812015.
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