Skip to main content

Advertisement

SpringerLink
Log in

Angiogenic patterns and their quantitation in high grade astrocytic tumors

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Background

The objectives of this study on high grade astrocytic tumors were (i) to establish differences, if any, between grades III & IV tumors among angiogenic parameters, both qualitative and quantitative, and (ii) to correlate angiogenic parameters with proliferation indices, namely T2a and MIB1 labeling indices.

Design

Twenty nine consecutive cases of WHO grades III (11) and IV (18) astrocytic tumors diagnosed in the year-2004 were studied, using H&E and CD34, MIB1 and T2a immunostaining by streptavidin biotin technique. Angiogenic patterns were studied and parameters quantitated using Image Pro Plus software (four hotspots) on CD34 immunostained sections to determine intratumoral microvessel density (iMVD), microvascular area (MVA), aspect, mean diameter (MD) and fractal dimension (FD).

Results

Main angiogenic patterns of capillary (18) and glomeruloid (9) types were best developed in glioblastomas. Statistically significant differences (P<0.05) were seen between grades III and IV in iMVD, aspect, MD and FD, but not in angiogenic patterns or MVA (P = 0.27). Statistically significant differences (P<0.05) were seen between glioblastomas with glomeruloid vs. capillary types in iMVD and FD, but not in MVA, aspect and mean vessel diameter. T2a values correlated with MIB1 labeling indices (R = 0.965, P<0.001). Intratumoral endothelial MIB1 LI was significantly higher in grade IV as compared to grade III, but did not correlate with angiogenic parameters. No correlation of angiogenic patterns and proliferation indices was noted (R = −0.221, P = 0.26). Limited follow up data showed all recurrent grade IV tumors to be of glomeruloid type.

Conclusion

Increased angiogenesis in grade IV, as compared to grade III, astrocytic tumors is characterized by an increased number/density of vessels: an increase in vessels characterized by disproportionate lengthening and likely associated with the infiltrative properties of the tumors; and an increase in pliable, irregularly shaped or structured vessels. In addition, there is a greater frequency of glomeruloid structures indicating inadequate directional migration of the newly formed vessels. The lack of correlation of these angiogenesis parameters with the MIB1 and T2a proliferation indices reflects the complexity of angiogenesis parameters in high grade gliomas. Further studies are needed to determine the usefulness of the angiogenic parameters in the improved diagnosis (grading) and prognosis of astrocytic tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brem S The role of vascular proliferation in the growth of brain tumors Clin Neurosurg 1976; 23:440–453

    PubMed  CAS  Google Scholar 

  2. Korkolopoulou P, Patsouris E, Kavantzas N, Konstantinidou AE, Christodoulou P, Thomas-Tsagli E, Pananikolaou A, Eftychiadis C, Pavlopoulos PM, Angelidakis D, Rologis D, Davaris P Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms Neuropathol Appl Neurobiol 2002; 28:57–66

    Article  PubMed  CAS  Google Scholar 

  3. Plate KH, Breier G, Risau W Molecular mechanisms of developmental and tumor angiogenesis Brain Pathol 1994; 4:207–218

    Article  PubMed  CAS  Google Scholar 

  4. Kleihues P, Cavenee W 2000 Pathology and Genetics of Tumors of Nervous System. World Health Organization Classification of Tumors IARC Press Lyon pp 10–54

    Google Scholar 

  5. Kleihues P, Burger PC, Scheithauer BW The new WHO classification of brain tumors Brain Pathol 1993; 3:255–268

    Article  PubMed  CAS  Google Scholar 

  6. Abdulrauf SL, Evardsen K, Ho KL, Yang XY, Rock JP, Rosenblum ML Vascular endothelial growth factor expression and vascular density as prognostic markers of survival in patients with low-grade astrocytoma J Neurosurg 1998; 88:513–520

    Article  PubMed  CAS  Google Scholar 

  7. Leon SP, Folkerth RD, Black PM Microvessel density is a prognostic indicator for patients with astroglial brain tumors Cancer 1996; 77:362–372

    Article  PubMed  CAS  Google Scholar 

  8. Folkerth RD Descriptive analysis and quantification of angiogenesis in human brain tumors J Neurooncol 2000; 50:165–172

    Article  PubMed  CAS  Google Scholar 

  9. Birner P, Piribauer M, Fischer I, Gatterbauer B, Marosi C, Ambros PF, Ambros IM, Bredel M, Oberhuber G, Rossler K, Budka H, Harris AL, Hainfellner JA Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: evidence for distinct angiogenic subtypes Brain Pathol 2003; 13:133–143

    Article  PubMed  CAS  Google Scholar 

  10. Taniguchi K, Wakabayashi T, Yoshida T et al. Immunohistochemical staining of DNA topoisomerase II alpha in human gliomas J Neurosurg 1999; 91:477–482

    PubMed  CAS  Google Scholar 

  11. Park S-H, Suh Y-L Expression of cyclin A and topoisomerase II alpha of oligodendrogliomas is correlated with tumor grade, MIB-1 labelling index and survival Histopathology 2003; 42:395–402

    Article  PubMed  Google Scholar 

  12. Weidner N, Semple JP, Welch WR, Folkman J Tumour angiogenesis and metastasis – correlation in invasive breast carcinoma. N Eng J Med 1991; 324:1–8

    Article  CAS  Google Scholar 

  13. Sharma S, Sharma MC, Sarkar C Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis Histopathology 2005; 46 : 481–489

    Article  PubMed  CAS  Google Scholar 

  14. Nelson DF, Curran WJ, Scott C, Nelson JS, Weinstein AS, Ahmad K Constine LS, Murray K, Powlis WD, Mohiuddin M, Fischbach J Hyperfractionated radiation therapy and bischlorethyl nitrosurea in the treatment of malignant glioma: possible advantage observed at 72.0 Gy in 1.2 BID fractions: report of the radiation therapy oncology group protocol 8302 Int J Radiat Oncol Biol Phys 1993; 25:193–207

    PubMed  CAS  Google Scholar 

  15. Curran WJ, Scott CB, Horton J, Nelson JS, Weinstein AS, Flschbach AJ Chang CH, Rotman M, Asbell SO, Krisch RE, Nelson DF. Recursive partitioning analysisof prognostic factors in three radiation therapy oncology group trials J Natl Cancer Inst 1993; 85:704–710

    Article  PubMed  Google Scholar 

  16. Winger MJ, McDonald DR, Cairncross JG Supratentorial anaplastic gliomas in adults: the prognostic importance of extent of resection and prior low-grade glioma J Neurosurg 1989; 71:487–493

    PubMed  CAS  Google Scholar 

  17. Weidner N The importance of tumour angiogenesis. The evidence continues to grow Am J Clin Pathol 2004; 122:675–677

    Article  PubMed  Google Scholar 

  18. Uzzan B, Nicolas P, Cucherat M, Perret GY Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis Cancer Res 2004; 64:2941–2955

    Article  PubMed  CAS  Google Scholar 

  19. Macchiarini P, Fontaini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovasculature to metastasis of non-small lung cancer Lancet 1992; 340:145–146

    Article  PubMed  CAS  Google Scholar 

  20. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J Tumour angiogenesis correlates with metastasis in invasive prostate carcinoma Am J Pathol 1993; 143:401–409

    PubMed  CAS  Google Scholar 

  21. Korkolopoulou P, Apostolidou E, Pavlopoulos PM, Kavantzas N, Vyniou N, Thymara I, Terpos E, Patsouris E, Yataganas X, Davaris P Prognostic evaluation of the microvascular network in myelodysplastic syndromes Leukemia 2001; 15:1369–1376

    Article  PubMed  CAS  Google Scholar 

  22. Korkolopoulou P, Viniou N, Kavantzas N, Patsouris E, Thymara I, Pavlopoulos PM, Terpos E, Stamatopoulos K, Plata E, Anargyrou K, Androulaki A, Davaris P, Yataganas X Clinicopathologic correlations of bone marrow angiogenesis in chronic myeloid leukemia: a morphometric study Leukemia 2003; 17:89–97

    Article  PubMed  CAS  Google Scholar 

  23. Srivastava A, Laidler P, Davies R, Horgan K, Hughes LE The prognostic significance of tumour vascularity in intermediate-thickness (0.76–4.0 mm thick) skin melanoma Am J Pathol 1986; 133:419–423

    Google Scholar 

  24. Wakui S, Furusato M, Itoh T Sasaki H, Akiyama A, Kinoshita I, Asano K, Tokuda T, Aizawa S, Ushigome S Tumour angiogenesis in prostate carcinoma with and without bone marrow metastasis: a morphometric study J Pathol 1992; 168:257–262

    Article  PubMed  CAS  Google Scholar 

  25. Wesseling P, Ruiter DJ, Burger PC Angiogenesis in brain tumors; pathobiological and clinical aspects J Neuro-oncol 1997; 32:253–265

    Article  CAS  Google Scholar 

  26. Sharma S, Karak AK, Sarker C, Gomathy G, Banerji AK, Schmitt HP A grading study of gliomas using computer aided malignancy classification and histologic morphometry J Neurooncol 1996; 27:75–85

    Article  PubMed  CAS  Google Scholar 

  27. Wesseling P, Van Der Laak J, De Leeuw H, Ruiter DJ, Burger PC Quantitative immunohistochemical analysis of the microvasculature in untreated human glioblastoma multiforme J Neurosurg 1994; 81:902–909

    Article  PubMed  CAS  Google Scholar 

  28. Schmitt HP, Oberwittler C Computer aided classification of malignancy in astrocytomas: II. The value of categorically evaluating histologic and non-histologic features for a numerical classifier Analyt Cell Pathol 1992; 4:409–419

    CAS  Google Scholar 

  29. Sharma S, Karak AK, Singh R, Mehta VS, Sarkar C, Schmitt HP A correlative study of gliomas using in vivo bromodeoxyuridine labeling index and computer aided malignancy grading Path Oncol Res 1999; 5:134–141

    Article  CAS  Google Scholar 

  30. Wesseling P, Vandersteenhoven JJ, Downey BT, Ruiter DJ, Burger PC Cellular components of microvascular proliferation in human glial and metastatic brain neoplasms. A light microscopic and immunohistochemical study of formalin-fixed, routinely processed material Acta Neuropathol 1993; 85:508–514

    Article  PubMed  CAS  Google Scholar 

  31. Stockhammer G, Obwegeser A, Kostron H, Schumacher P, Muigg A, Felber S, Maier H, Slavc I, Gunsilius E, Gastl G Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression Acta Neuropathol 2000; 100:101–105

    Article  PubMed  CAS  Google Scholar 

  32. Gesundheit B, Klement G, Senger C, Kerbel R, Kieran M, Baruchel S, Becker L Differences in vasculature between pilocytic and anaplastic astrocytomas of childhood Med Pediatr Oncol 2003; 41:516–526

    Article  PubMed  Google Scholar 

  33. Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D Angiogenesis in gliomas: biology and molecular pathophysiology Brain Pathol 2005; 15:297–310

    Article  PubMed  CAS  Google Scholar 

  34. Schiffer D, Chio A, Mauro GA, Migheli A, Vigliani MC The vascular response to tumor infiltration in malignant gliomas Acta Neuropathol 1989; 77:369–378

    Article  PubMed  CAS  Google Scholar 

  35. Wesseling P, Van Der Laak J, Link M, Teepen H, Ruiter DJ Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy Hum Pathol 1998; 29:352–358

    Article  PubMed  CAS  Google Scholar 

  36. Dales JP, Garcia S, Carpentier S, Andrac L, Ramuz O, Lavaut MN, Allasia C, Bonnier P, Taranger-Charpin C Prediction of metastasis risk (11 year follow up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905) Br J Cancer 2004; 90:1216–1221

    Article  PubMed  CAS  Google Scholar 

  37. Watt P, Hickson ID Structure and function of type II DNA topoisomerases Biochem J 1994; 303:681–695

    PubMed  CAS  Google Scholar 

  38. Schneider E, Hsiang Y-H, Liu LF DNA topoisomerases as anti-cancer drug targets Adv Pharmacol 1990; 21:149–183

    Article  PubMed  CAS  Google Scholar 

  39. Konstantinidou AE, Patsouris E, Korkolopoulou P, Kavantzas N, Mahera H, Davaris P DNA topoisomerase II alpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas Histopathology 2001; 39:402–408

    Article  PubMed  CAS  Google Scholar 

  40. Wesseling P, Van Der Sanden G, Van Der Laak J, Teepen H, Verbeek A, De Wilde P: Prognostic value of microvascular parameters in diffuse astrocytic neoplasms (Abstract). J Neuropathol Exp Neurol 58: 535, 1999

    Google Scholar 

  41. Erdem O, Dursun A, Coskun U, Gunel N The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma Tumori 2005; 91:46–52

    PubMed  CAS  Google Scholar 

  42. Xu JL, Lai R, Kinoshita T, Nakashima N, Nagasaka T Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade J Clin Pathol 2002 Jul 55(7):530–534

    CAS  Google Scholar 

  43. Xiao L, Tang LD Significance of proliferating cell nuclear antigen (PCNA) index and microvessel density (MVD) in endometrial carcinoma Ai Zheng 2005; 24:19–22

    PubMed  CAS  Google Scholar 

  44. Jonjic N, Zamolo G, Stifter S, Fuckar D, Gruber F, Sasso F, Rizzardi C, Melato M Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanoma Clin Exp Dermatol. 2003; 28:310–314

    Article  PubMed  CAS  Google Scholar 

  45. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, Ishikawa S, Wada H Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis Lung Cancer 2003; 39:289–296

    Article  PubMed  Google Scholar 

  46. Diaz-Rubio JL, Duarte-Rojo A, Saqui-Salces M, Gamboa-Dominguez A, Robles-Diaz G Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors Arch Pathol Lab Med 2004; 128:426–429

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  48. Vidal S, Horvath E, Kovacs K, Lloyd RV, Scheithauer BW Microvascular structural entropy: a novel approach to assess angiogenesis in pituitary tumors Endocr Pathol 2003; 14:239–247

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We sincerely thank the Council of Scientific and Industrial Research, Pusa, New Delhi for supporting this research endeavor. We also thank Mr. Rajesh and Ms. Kiran from AIIMS for technical assistance, Mr. Rajvir (AIIMS) and Mr. Sanjay (TMC) for statistical analyses, Dr. Deepak Gupta from Neurosurgery (AIIMS) for providing follow up data, and Dr. Prabal Deb for moral support.

Author information

Authors and Affiliations

  1. Department of Pathology, All India Institute of Medical Sciences, 110029, New Delhi, India

    Suash Sharma, Mehar C. Sharma & Chitra Sarkar

  2. Department of Neurosurgery, All India Institute of Medical Sciences, 110029, New Delhi, India

    Deepak Kumar Gupta

  3. Department of Pathology, All India Institute of Medical Sciences, 110029, New Delhi, India

    Chitra Sarkar

Authors
  1. Suash Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mehar C. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deepak Kumar Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chitra Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chitra Sarkar.

Additional information

The study was presented at the 94th Annual Meeting of the United States and Canadian Academy of Pathology, March 2005 at San Antonio, TX. (Mod Pathol 2005; 18 (suppl.1): 295A)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, S., Sharma, M.C., Gupta, D.K. et al. Angiogenic patterns and their quantitation in high grade astrocytic tumors. J Neurooncol 79, 19–30 (2006). https://doi.org/10.1007/s11060-006-9120-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-006-9120-6

Keywords

Search

Navigation