Correlation between vascular endothelial growth factor (VEGF) expression with histopathological findings in osteosarcoma

https://doi.org/10.19106/JMedSci005302202101

Fikar Arsyad Hakim(1), Yuni Artha Prabowo Putro(2), Yudha Mathan Sakti(3), Rahadyan Magetsari(4), Irianiwati Widodo(5), Ery Kus Dwianingsih(6*)

(1) Departement of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada
(2) Division of Orthopaedics and Traumatology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
(3) Division of Orthopaedics and Traumatology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
(4) Division of Orthopaedics and Traumatology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
(5) Departement of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada
(6) Departement of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Vascular endothelial growth factor (VEGF) expression is associated with malignancy progression, metastasis, and poor prognosis in many malignancies, including osteosarcoma. However, studies concerning correlations between VEGF expression and histopathological prognostic factors ofosteosarcoma are limited. This study aimed to evaluate the correlations between VEGF expression and histopathological findings in osteosarcoma’spatients.This was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) samples of 32 osteosarcoma’s patients from Dr. Sardjito General Hospital, Yogyakarta. Histopathological findings of specimens were re-evaluated by two independent observers, recorded for the subtypes, invasiveness, grading, mitotic counts, and tumor infiltrating lymphocytes (TIL). Expression of VEGF was determined based on immunostaining and evaluated using immunoreactivity score (IRS).Chi-square and Spearman correlation test were used to analyze the association between variables. Range of VEGF expression score was 0 to 11, with mean 5.09. Significant negative correlation between the VEGF expression and TIL was observed (p=0.046). However, there was no significant correlations between the VEGF expression and osteosarcomas subtypes, invasion, grading or mitotic counts (p> 0.05). In conclusion, the VEGF expression is associated with TIL. Further study is needed to evaluate the roles of VEGF and lymphocytes in osteosarcoma development dan progression in order to better understand of the role of VEGF in immunotherapy of osteosarcoma.

Keywords


histopathological findings; osteosarcoma; VEGF; malignancies;TIL;

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References

  1. Marko TA, Diessner BJ, Spector LG. Prevalence of metastasis at diagnosis of osteosarcoma: an international comparison: prevalence of metastatic osteosarcoma at diagnosis. Pediatr Blood Cancer 2016; 63(6):1006-11. https://doi.org/10.1002/pbc.25963
  2. Xie L, Ji T, Guo W. Anti-angiogenesis target therapy for advanced osteosarcoma. Oncol Rep 2017; 38(2):625-36. https://doi.org/10.3892/or.2017.5735
  3. Prager GW, Poettler M, Unseld M, Zielinski CC. Angiogenesis in cancer: anti-VEGF escape mechanisms. Transl Lung Cancer Res 2012; 1(1):14-25. https://doi.org/10.3978/j.issn.2218-6751.2011.11.02
  4. Peng N, Gao S, Guo X, Wang G, Cheng C, Li M, et al. Silencing of VEGF inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via VEGF/PI3K/AKT signaling pathway. Am J Transl Res 2016; 8(2):1005-15.
  5. Lammli J, Fan M, Rosenthal HG, Patni M, Rinehart E, Vergara G, et al. Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma. Int Orthop 2012; 36(11):2307-13. https://doi.org/10.1007/s00264-012-1629-z
  6. Becker RG, Galia CR, Morini S, Viana CR. Immunohistochemical expression of VEGF and HER-2 proteins in osteosarcoma biopsies. Acta Ortop Bras 2013; 21(4):233-8. https://doi.org/10.1590/S1413-78522013000400010
  7. Chui MH, Kandel RA, Wong M, Griffin AM, Bell RS, Blackstein ME, et al. Histopathologic features of prognostic significance in high-grade osteosarcoma. Arch Pathol Lab Med 2016; 140(11):1231-42. https://doi.org/10.5858/arpa.2015-0389-OA
  8. Andreou D, Werner M, Pink D, Traub F, Schuler M, Gosheger G, et al. Prognostic relevance of the mitotic count and the amount of viable tumour after neoadjuvant chemotherapy for primary, localised, high-grade soft tissue sarcoma. Br J Cancer 2015; 112(3):455–60. https://doi.org/10.1038/bjc.2014.635
  9. Wang Z, Li B, Ren Y, Ye Z. T-Cell-Based immunotherapy for osteosarcoma: challenges and opportunities. Front Immunol 2016; 7:353. https://doi.org/10.3389/fimmu.2016.00353
  10. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013.
  11. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26(2):259-71. https://doi.org/10.1093/annonc/mdu450
  12. Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue – a review. Diagn Pathol 2014; 9(1):221. https;//doi.org/10.1186/s13000-014-0221-9
  13. Schapira L, Altman J, Berek J, Cohen E, Dale W, Ghobrial I, et al. Osteosarcoma - Childhood and Adolescence. Cancer.net. 2019. Available from: https://www.cancer.net/cancer-types/osteosarcoma-childhood/view-all
  14. Marko TA, Diessner BJ, Spector LG. Prevalence of metastasis at diagnosis of osteosarcoma: an international comparison: prevalence of metastatic osteosarcoma at diagnosis. Pediatr Blood Cancer 2016; 63(6):1006-11. https://doi.org/10.1002/pbc.25963
  15. Yu X-W, Wu T-Y, Yi X, Ren W-P, Zhou Z, Sun Y, et al. Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis. Tumor Biol 2014; 35(1):155–60. https://doi.org/10.1007/s13277-013-1019-1
  16. Huang H, Langenkamp E, Georganaki M, Loskog A, Fuchs PF, Dieterich LC, et al. VEGF suppresses T-lymphocyte infiltration in the tumor microenvironment through inhibition of NF-κB-induced endothelial activation. FASEB J 2015; 29(1):227-38. https://doi.org/10.1096/fj.14-250985
  17. Shen JK, Cote GM, Choy E, Yang P, Harmon D, Schwab J, et al. Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol Res 2014; 2(7):690-8. https://doi.org/10.1158/2326-6066.CIR-13-0224
  18. Butters O, Young K, Cunningham D, Chau I, Starling N. Targeting vascular endothelial growth factor in oesophagogastric cancer: a review of progress to date and immunotherapy combination strategies. Front Oncol 2019; 9:618. https://doi.org/10.3389/fonc.2019.00618
  19. Mizobuchi H, García-Castellano JM, Philip S, Healey JH, Gorlick R. Hypoxia markers in human osteosarcoma: an exploratory study. Clin Orthop 2008; 466(9):2052-9. https://doi.org/10.1007/s11999-008-0328-y
  20. Park HR, Min K, Kim HS, Jung WW, Park YK. Expression of vascular endothelial growth factor-C and its receptor in osteosarcomas. Pathol Res Pract 2008; 204(8):575-82. https://doi.org/10.1016/j.prp.2008.01.015
  21. Daft PG, Yang Y, Napierala D, Zayzafoon M. The growth and aggressive behavior of human osteosarcoma is regulated by a camkii-controlled autocrine vegf signaling mechanism. PLoS One 2015; 10(4):e0121568. https://doi.org/10.1371/journal.pone.0121568



DOI: https://doi.org/10.19106/JMedSci005302202101

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