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Clinical correlation of molecular (VEGF, FGF, PDGF, c-Myc, c-Kit, Ras, p53) expression in juvenile nasopharyngeal angiofibroma

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Background

A molecular surrogate may exist for the clinical behaviour of juvenile nasopharyngeal angiofibroma (JNA).

Methods

In 9–14 cases, a ‘correlation’ of clinical behaviour with molecular expression (m-RNA expression through RT-PCR) of VEGF, FGF, PDGF, Ras, c-Myc, c-Kit and p53 was undertaken.

Results

A comparison of the two extremes of expressions characterized some specific clinical phenotypes for every marker except c-Myc. A higher FGF was associated with post-adolescent presentation, smaller tumour size, enhanced haemorrhage and recurrence. A higher c-Kit was associated with adolescents, rapid growth, skull base involvement and recurrence. Enhanced Ras was associated with post-adolescence, smaller tumour size, skull base involvement and recurrence. Enhanced p53 and PDGF were associated with adolescents, early presentation and rapid progression. Higher VEGF expression was associated with skull base involvement and enhanced haemorrhage.

Conclusion

This study is currently the only evidence revealing a clinical molecular association in JNA and larger multicentric studies need to be performed to show a statistical significance.

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References

  1. Schuon R, Brieger J, Heinrich UR, Roth Y, Szyfter W, Mann WJ (2007) Immunohistochemical analysis of growth mechanisms in juvenile angiofibroma. Eur Arch Otorhinolaryngol 264:389–394

    Article  Google Scholar 

  2. Schiff M, Gonzalez AM, Ong M, Baird A (1992) Juvenile nasopharyngeal angiofibroma contain an angiogenic growth factor: basic FGF. Laryngoscope 102:940–945

    Article  CAS  Google Scholar 

  3. Dillard DG, Cohen C, Muller S, Del Gaudio J, Reichman O, Parrish B et al (2000) Immunolocalization of activated transforming growth factor beta1 in juvenile nasopharyngeal angiofibroma. Arch Otolaryngol Head Neck Surg 126:723–725

    Article  CAS  Google Scholar 

  4. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    Article  CAS  Google Scholar 

  5. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735–745

    Article  CAS  Google Scholar 

  6. Herzog B, Pellet-Many C, Britton G, Hartzoulakis B, Zachary IC (2011) VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. Mol Biol Cell 22:2766–2776

    Article  CAS  Google Scholar 

  7. Palmer BF, Clegg DJ (2014) Oxygen sensing and metabolic homeostasis. Mol Cell Endocrinol 397:51–58

    Article  CAS  Google Scholar 

  8. Matsumoto E, Sasaki S, Kinoshita H, Kito T, Ohta H, Konishi M et al (2013) Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16. Genes Cells 18:544–553

    Article  CAS  Google Scholar 

  9. Xiao L, Du Y, Shen Y, He Y, Zhao H, Li Z (2012) TGF-beta 1 induced fibroblast proliferation is mediated by the FGF-2/ERK pathway. Front Biosci (Landmark Ed) 17:2667–2674

    Article  Google Scholar 

  10. Warburton D (2012) Developmental responses to lung injury: repair or fibrosis. Fibrogenesis Tissue Repair 5:S2

    Article  Google Scholar 

  11. Gupte VV, Ramasamy SK, Reddy R, Lee J, Weinreb PH, Violette SM et al (2009) Overexpression of fibroblast growth factor-10 during both inflammatory and fibrotic phases attenuates bleomycin induced pulmonary fibrosis in mice. Am J Respir Crit Care Med 180:424–436

    Article  CAS  Google Scholar 

  12. Lemmon SK, Riley MC, Thomas KA, Hoover GA, Maciag T, Bradshaw RA (1982) Bovine fibroblast growth factor: comparison of brain and pituitary preparations. J Cell Biol 95:162–169

    Article  CAS  Google Scholar 

  13. Thomas KA, Rios-Candelore M, Gimenez-Gallego G, DiSalvo J, Bennett C, Rodkey J et al (1985) Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. Proc Natl Acad Sci USA 82:6409–6413

    Article  CAS  Google Scholar 

  14. Schreiber AB, Kenney J, Kowalski WJ, Friesel R, Mehlman T, Maciag T (1985) Interaction of endothelial cell growth factor with heparin: characterization by receptor and antibody recognition. Proc Natl Acad Sci USA 82:6138–6142

    Article  CAS  Google Scholar 

  15. Schreiber AB, Kenney J, Kowalski J, Thomas KA, Gimenez-Gallego G, Rios-Candelore M et al (1985) A unique family of endothelial cell polypeptide mitogens: the antigenic and receptor cross-reactivity of bovine endothelial cell growth factor, brain-derived acidic fibroblast growth factor, and eye-derived growth factor-II. J Cell Biol 101:1623–1626

    Article  CAS  Google Scholar 

  16. Kumar V (2010) Robbins and coltran pathologic basis of disease. Elsevier, Beijing, pp 88–89 (ISBN: 978-1-4160-3121-5)

  17. Demoulin JB, Montano-Almendras CP (2012) Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis. Am J Blood Res 2:44–56

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276–1312

    Article  CAS  Google Scholar 

  19. Hannink M, Donoghue DJ (1989) Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim Biophys Acta 989:1–10

    CAS  PubMed  Google Scholar 

  20. Heldin CH (1992) Structural and functional studies on platelet-derived growth factor. EMBO J 11:4251–4259

    Article  CAS  Google Scholar 

  21. Zhang PJ, Weber R, Liang H, Pasha TL, LiVolsi VA (2003) Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps. Arch Pathol Lab Med 127:1480–1484

    CAS  PubMed  Google Scholar 

  22. Pauli J, Gundelach R, Vanelli-Rees A, Rees G, Campbell C, Dubey S et al (2008) Juvenile nasopharyngeal angiofibroma: an immunohistochemical characterisation of the stromal cell. Pathology 40:396–400

    Article  CAS  Google Scholar 

  23. Ribatti D, Ranieri G, Basile A, Azzariti A, Paradiso A, Vacca A (2012) Tumor endothelial markers as a target in cancer. Expert Opin Ther Targets 16:1215–1225

    Article  CAS  Google Scholar 

  24. Downward J (2003) Targeting RAS signaling pathways in cancer therapy. Nat Rev Cancer 3:11–22

    Article  CAS  Google Scholar 

  25. Lim KH, Baines AT, Fiordalisi JJ, Shipitsin M, Feig LA, Cox AD et al (2005) Activation of RalA is critical for Ras-induced tumorigenesis of human cells. Cancer Cell 7:533–545

    Article  CAS  Google Scholar 

  26. Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT,.et al (2002) Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev 16:2045–2057

    Article  CAS  Google Scholar 

  27. Paterson IC, Eveson JW, Prime SS (1996) Molecular changes in oral cancer may reflect aetiology and ethnic origin. Eur J Cancer B Oral Oncol 32:150–153

    Article  Google Scholar 

  28. Mishra A, Mishra SC (2016) Changing trends in the incidence of juvenile nasopharyngeal angiofibroma: seven decades of experience at King George’s Medical University, Lucknow, India. J Laryngol Otol 130:363–368

    Article  CAS  Google Scholar 

  29. Mishra A, Jaiswal R, Pandey A, Mishra SC (2018) Molecular interactions in juvenile nasopharyngeal angiofibroma: preliminary signature and relevant review. Eur Arch Otolaryngol (submitted)

  30. Pandey P, Mishra A, Tripathi AM, Verma V, Trivedi R, Singh HP et al (2017) Current molecular profile of juvenile nasopharyngeal angiofibroma: first comprehensive study from India. Laryngoscope 127:e100–e106

    Article  CAS  Google Scholar 

  31. Mishra A, Mishra SC, Verma V, Singh HP, Kumar S, Tripathi AM et al (2016) In defence of transpalatal, transpalatal-circumaxillary (transpterygopalatine) and transpalatal-circumaxillary-sublabial approaches to lateral extensions of juvenile nasopharyngeal angiofibroma. J Laryngol Otol 130:462–473

    Article  CAS  Google Scholar 

  32. Radkowski D, McGill T, Healy GB, Ohlms L, Jones DT (1996) Angiofibroma: changes in staging and treatment. Arch Otolaryngol Head Neck Surg 122:122–129

    Article  CAS  Google Scholar 

  33. Mishra SC, Shukla GK, Bhatia N, Pant MC (1989) A rational classification of angiofibromas of the postnasal space. J Laryngol Otol 103:912–916

    Article  CAS  Google Scholar 

  34. Mishra A, Mishra SC, Pandey A (2017) Variations in molecular expressions of juvenile nasopharyngeal angiofibroma. J Laryngol Otol 131(9):752–759

    Article  CAS  Google Scholar 

  35. Mishra A, Verma V (2018) Implication of embolization in residual disease in lateral extension of juvenile nasopharyngeal angiofibroma. J Oral Biol Craniofacial Res (submitted)

  36. Saylam G, Yucel OT, Sungur A, Onerci M (2006) Proliferation, angiogenesis and hormonal markers in juvenile nasopharyngeal angiofibroma. Int J Pediatr Otorhinolaryngol 70:227–234

    Article  Google Scholar 

  37. Brieger J, Wierzbicka M, Sokolov M, Roth Y, Szyfter W, Mann WJ (2004) Vessel density, proliferation and immunolocalization of vascular endothelial growth factor in juvenile nasopharyngeal angiofibromas. Arch Otolaryngol Head Neck Surg 130:727–731

    Article  Google Scholar 

  38. Arbiser ZK, Arbiser JL, Cohen C, Gal AA (2001) Neuroendocrine lung tumors: grade correlates with proliferation but not angiogenesis. Mod Pathol 14:1195–1199

    Article  CAS  Google Scholar 

  39. Juric G, Zarkovic N, Nola M, Tillian M, Jukić S (2001) The value of cell proliferation and angiogenesis in the prognostic assessment of ovarian granulosa cell tumors. Tumori 87:47–53

    Article  CAS  Google Scholar 

  40. Mishra A, Singh V, Verma V, Pandey S, Trivedi R, Singh HP et al (2016) Current status and Clinical correlation of beta-catenin in juvenile nasopharyngeal angiofibroma. J Laryngol Otol 30:1–7

    Google Scholar 

  41. Profumo V, Gandellini P (2013) MicroRNAs: cobblestones on the road to cancer metastasis. Crit Rev Oncog 18:341–355

    Article  Google Scholar 

  42. Pietras K, Pahler J, Bergers G, Hanahan D (2008) Functions of paracrine PDGF signalling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 5:e19

    Article  Google Scholar 

  43. Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G (2005) PDGFRbþ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879

    Article  CAS  Google Scholar 

  44. Dong J, Grunstein J, Tejada M, Peale F, Frantz G, Liang WC et al (2004) VEGF null cells require PDGFR alpha signaling mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 23:2800–2810

    Article  CAS  Google Scholar 

  45. Nagai MA, Butugan O, Logullo A, Brentani MM (1996) Expression of growth factors, protooncogenes and p53 in nasopharyngeal angiofibromas. Laryngoscope 106:190–195

    Article  CAS  Google Scholar 

  46. López-Martin A, Ballestín C, Garcia-Carbonero R, Castaño A, Lopez-Ríos F, López-Encuentra A et al (2007) Prognostic value of Kit expression in small cell lung cancer. Lung Cancer 56:405–413

    Article  Google Scholar 

  47. Chau WK, Ip CK, Mak AS, Lai HC, Wong AS (2013) c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/β-catenin-ATP-binding cassette G2 signaling. Oncogene 32:2767–2781

    Article  CAS  Google Scholar 

  48. Wiesner C, Nabha SM, Dos Santos EB, Yamamoto H, Meng H, Melchior SW et al (2008) c-Kit and its ligand stem cell factor: potential contribution to prostate cancer bone metastasis. Neoplasia 10:996–1003

    Article  CAS  Google Scholar 

  49. Cheng P, Chen H, Liu SR, Pu XY (2013) A ZC. SNPs in KIT and KITLG genes may be associated with oligospermia in Chinese population. Biomarkers 18:650–654

    Article  CAS  Google Scholar 

  50. Marcu KB, Bossone SA, Patel AJ (1992) Myc function and regulation. Annu Rev Biochem 61:809–860

    Article  CAS  Google Scholar 

  51. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512

    Article  CAS  Google Scholar 

  52. van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A et al (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241–250

    Article  Google Scholar 

  53. Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H, Newton IP et al (2004) Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation and migration. Genes Dev 18:1385–1390

    Article  CAS  Google Scholar 

  54. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic Ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602

    Article  CAS  Google Scholar 

  55. Mitchell PJ, Perez-Nadales E, Malcolm DS, Lloyd AC (2003) Dissecting the contribution of p16(INK4A) and the Rb family to the Ras transformed phenotype. Mol Cell Biol 23:2530–2542

    Article  CAS  Google Scholar 

  56. Coutinho CM, Bassini AS, Gutie´rrez LG, Butugan O, Kowalski LP, Brentani MM et al (1999) Genetic alterations in Ki-ras and Ha-ras genes in juvenile nasopharyngeal angiofibromas and head and neck cancer. Sao Paulo Med J 117:113–120

    Article  CAS  Google Scholar 

  57. Schick B, Veldung B, Wemmert S, Jung V, Montenarh M, Meese E et al (2005) p53 and Her-2/neu in juvenile angiofibromas. Oncol Rep 13:453–457

    CAS  PubMed  Google Scholar 

  58. Mishra A, Sachadeva M, Jain A, Shukla NM, Pandey A (2016) Human papilloma virus in juvenile nasopharyngeal angiofibroma: possible recent trend. Am J Otolaryngol Head Neck Med Surg 37:317–322

    Google Scholar 

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Acknowledgements

The principal author would like to acknowledge Praveen Pandey from CDRI for his efforts in generating the necessary laboratory data and while the basic molecular expression values have been published in the laryngoscope, the current study exclusively correlates the clinical parameters.

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Correspondence to Anupam Mishra.

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This article is a part of the PhD work of Dr. Anupam Mishra.

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Mishra, A., Mishra, S.C., Tripathi, A.M. et al. Clinical correlation of molecular (VEGF, FGF, PDGF, c-Myc, c-Kit, Ras, p53) expression in juvenile nasopharyngeal angiofibroma. Eur Arch Otorhinolaryngol 275, 2719–2726 (2018). https://doi.org/10.1007/s00405-018-5110-5

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  • DOI: https://doi.org/10.1007/s00405-018-5110-5

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