Prognostic and Survival-Related Factors in Patients with Well-Differentiated Oligodendrogliomas

 

 Buy Article Permissions and Reprints

Abstract

Oligodendrogliomas are brain tumors with unpredictable biological and clinical behavior. Prognostic factors related to survival are still controversial. The present study reviews 50 patients with well-differentiated (WHO grade II) oligodendrogliomas, located in the cerebral hemispheres and operated upon between 1980 and 1998. Prognostic factors studied include patient's age and sex, tumor location and extent, preoperative KPS, and extent of the surgical resection. The Ki-67 and the proliferative cell nuclear antigen (PCNA) levels were studied in all patients and some growth factors (GFs), including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and tenascine were examined in 20 patients. The long-term outcome and survival are not significantly correlated with the patient's age and sex, tumor location and extent, preoperative KPS and procedure for resection. Patients with lower Ki-67 and PCNA showed a significantly longer survival time (p < 0.001 and p < 0.019, respectively). Between 45 and 70 % of the tumors stained positive for one or more growth factors. Interestingly, cases with late recurrences (more than 4 years after surgery) and longer survival are significantly associated to negative GF expression or slight positivity, as compared with the variable and more often moderate immunoreactivity of cases with early anaplastic recurrences and shorter survival time. The presented data suggest that low proliferation indices and negative GF expression are associated with longer survival in well-differentiated oligodendrogliomas.

Zusammenfassung

Fragestellung: Oligodendrogliome sind Hirntumoren mit schwer vorhersehbarem biologischen und klinischen Verhalten. Prognostische Faktoren, die das Überleben beeinflussen, sind nach wie vor umstritten. Diese Studie analysiert 50 Patienten mit gut differenzierten WHO Grad-II-Oligodendrogliomen, die in den zerebralen Hemisphären lokalisiert waren und zwischen 1980 und 1998 opereriert wurden. Methoden: Die untersuchten prognostischen Faktoren schließen ein: Alter, Geschlecht, Tumorlokalisation, Tumorausdehnung, präoperativer Karnofsky-Score (KPS) und Ausmaß der Resektion. Bei allen Patienten wurde das Ki-67 und das PCNA (proliferatives Zellnuklear-Antigen) untersucht und bei einigen die Wachstumsfaktoren, einschließlich Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF) und Tenascin bei 20 Patienten. Ergebnisse: Überleben und Langzeitergebnisse sind nicht signifikant mit dem Alter des Patienten und dem Geschlecht, der Lokalisation des Tumors, der Tumorausdehnung, dem präoperativen KPS und dem Ausmaß der Resektion korreliert. Patienten, die ein niedriges Ki-67 und PCNA aufwiesen, zeigten eine deutlich längere Überlebenszeit (p < 0,001 beziehungsweise p > 0,019). Zwischen 45 und 70 % der Tumoren wiesen eine Anfärbung für einen oder mehrere Wachstumsfaktoren auf. Interessanterweise waren Tumoren mit späten Rezidiven (mehr als 4 Jahre nach Operation) und längerer Überlebenszeit signifikant assoziiert mit einer negativen Wachstumsfaktor-Expression oder nur leicht positiver Expression, verglichen mit der variablen und oft mäßigen Immunreaktivität der Fälle, die ein frühes anaplastisches Rezidiv und kürzere Überlebenszeiten aufwiesen. Schlussfolgerung: Diese Daten legen die Schlussfolgerung nahe, dass ein niedriger Proliferationsindex und negative Wachstumsfaktor-Expression mit längerem Überleben bei gut differenzierten Oligodendrogliomen assoziert sind.

References

• 1 Abdulrauf S I, Edvardsen K, Ho K L, Yang X Y, Rock J P, Rosenblum M L. 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
  PubMedGoogle Scholar
• 2 Berger M S, Deliganis A V, Dobbins J. et al . The effect of extent of resection on recurrence in patients with low-grade cerebral hemisphere gliomas.  Cancer. 1994;  74 1784-1791
  CrossrefPubMedGoogle Scholar
• 3 Burger P C, Rawlings C E, Cox E B, McLendon R E, Schold Jr  S C, Bullard D E. Clinicopathologic correlations in the oligodendroglioma.  Cancer. 1987;  59 1345-1352
  CrossrefPubMedGoogle Scholar
• 4 Burger P C, Scheithauer B W, Vogel F S. Surgical Pathology of the Nervous System and its Covering. 4th edn. Churchill-Livingstone, New York 2002; 234-235
  Google Scholar
• 5 Caincross J G, Meki K, Zlatescu M C. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas.  J Nat Cancer Inst. 1998;  90 1473-1479
  CrossrefPubMedGoogle Scholar
• 6 Celli P, Nofrone I, Palma L, Cantore G P, Fortuna A. Cerebral oligodendroglioma: prognostic factors and life history.  Neurosurgery. 1994;  35 1018-1034
  PubMedGoogle Scholar
• 7 Coons S W, Johnson P C, Pearl D K. The prognostic significance of Ki-67 labeling indices for oligodendrogliomas.  Neurosurgery. 1997;  41 878-885
  CrossrefPubMedGoogle Scholar
• 8 Daumas-Duport C, Tucker M L, Kolles H, Cervera P, Beuvon F, Varlet P, Udo N, Koziak M, Chodkiewicz J P. Oligodendrogliomas. Part II: A new grading system based on morphological and imaging criteria.  J Neurooncol. 1997;  34 61-78
  CrossrefPubMedGoogle Scholar
• 9 Dehghani F, Schachenmayr W, Laun A, Korf H W. Prognostic implications of histopathological, immunohistochemical and clinical features of oligodendrogliomas: a study of 89 cases.  Acta Neuropathol (Berl). 1998;  95 493-504
  CrossrefPubMedGoogle Scholar
• 10 Di Rocco F, Carroll R S, Zhang J, Black P M. Platelet-derived growth factor and its receptor expression in human oligodendrogliomas.  Neurosurgery. 1998;  42 341-346
  PubMedGoogle Scholar
• 11 Engelhard H H, Stelea A, Cochran E J. Oligodendroglioma: pathology and molecular biology.  Surg Neurol. 2002;  58 111-117
  CrossrefPubMedGoogle Scholar
• 12 Engelhard H H, Stelea A C. Oligodendroglioma: clinical features, treatment and prognosis.  Surg Neurol. 2003;  60 443-455
  CrossrefPubMedGoogle Scholar
• 13 Ganju V, Jenkins R B, O'Fallon J R. Prognostic factors in gliomas: a multivariate analysis of clinical, pathologic, flow cytometric, cytogenetic, and molecular markers.  Cancer. 1994;  74 920-927
  CrossrefPubMedGoogle Scholar
• 14 Giannini C, Scheithauer B W, Weaver M S, Burger P C, Kros J M, Mork S, Groeber M B, Bausermann S, Buckman J C, Buton J, Riepe R, Tazelaar H D, Nascimento A G, Gotty T, Keeney G L, Pernicone P, Altermatt I. Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading.  J Neuropathol Exp Neurol. 2001;  60 248-262
  PubMedGoogle Scholar
• 15 Heegard S, Sommer H M, Broholm H, Broendstrup O. Proliferating cell nuclear antigen and Ki-67 immunohistochemistry of oligodendrogliomas with special reference to prognosis.  Cancer. 1995;  76 1809-1813
  CrossrefPubMedGoogle Scholar
• 16 Korshunov A, Golanov A, Sycheva R. Immunohistochemical markers for prognosis of oligodendroglial neoplasms.  J Neurooncol. 2002;  58 237-253
  CrossrefPubMedGoogle Scholar
• 17 Korshunov A, Golanov A. The prognostic significance of vascular endothelial growth factor (VEGF C-1) immunoexpression in oligodendroglioma. An analysis of 91 cases.  J Neurooncol. 2000;  48 13-19
  CrossrefPubMedGoogle Scholar
• 18 Kros J M, Hop W C, Godschalk J J, Krishnadath K K. Prognostic value of the proliferation-related antigen Ki-67 in oligodendrogliomas.  Cancer. 1996;  78 1107-1113
  CrossrefPubMedGoogle Scholar
• 19 Kros J M, Pieterman H, Van Eden C G. et al . Oligodendroglioma: the Rotterdam-Dijkaigt experience.  Neurosurgery. 1994;  34 959-966
  PubMedGoogle Scholar
• 20 Kros J M, Zheng P, Wolbers G J, Van der Bent M J. Oligodendroglial tumors. In: Berger MS, Prados MD (eds). Textbook of Neuro-Oncology. Elsevier Saunders, Philadelphia 2005; chap 23: 163-176
  Google Scholar
• 21 Leon S P, Folkerth R D, Black P M. Microvessel density is a prognostic indicator for patients with astroglial brain tumors.  Cancer. 1996;  77 362-372
  CrossrefPubMedGoogle Scholar
• 22 Lindergaard K F, Mork S J, Eide G E, Halvorsen T B, Hatlevoli R, Solgaard T, Dahl O, Ganz J. Statistical analysis of clinicopathological features, radiotherapy, and survival in 170 cases of oligodendroglioma.  J Neurosurg. 1987;  67 224-230
  PubMedGoogle Scholar
• 23 Mork S J, Lindegaard K F, Halvorsen T B, Lehmann E H, Solgaard T, Hatlevoli R, Harvei S, Ganz J. Oligodendroglioma: incidence and biological behavior in a defined population.  J Neurosurg. 1985;  63 881-889
  PubMedGoogle Scholar
• 24 Mork S J, Halvorsen T B, Lindegaard K F, Elde E. Oligodendroglioma. Histologic evaluation and prognosis.  J Neuropathol Exp Neurol. 1986;  45 65-78
  PubMedGoogle Scholar
• 25 Muemmer W, Hartmann C, Hoffmann A. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets.  Am J Pathol. 2002;  161 313-319
  PubMedGoogle Scholar
• 26 Pietsch T, Valter M M, Wolf H K, Deimling A von, Huang H J, Cavenee W K, Wiestler O D. Expression and distribution of vascular endothelial growth factor protein in human brain tumors.  Acta Neuropathol (Berl). 1997;  93 109-117
  CrossrefPubMedGoogle Scholar
• 27 Prayson R A, Mohan D S, Song P, Suh J H. Clinicopathologic study of forty-four histologically pure supratentorial oligodendrogliomas.  Ann Diagn Pathol. 2000;  4 218-227
  PubMedGoogle Scholar
• 28 Reifenberger J, Ring G U, Gies U, Cobbers L, Oberstrass J, An H X, Niederhacher D, Wechsler W, Reifenberger G. Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression.  J Neuropathol Exp Neurol. 1996;  55 822-831
  PubMedGoogle Scholar
• 29 Reis-Filho J S, Faoro L N, Carrilho C, Bleggi-Torres L F, Schmitt F C. Evaluation of cell proliferation, epidermal growth factor receptor, and bcl-2 immunoexpression as prognostic factors for patients with World Health Organization grade 2 oligodendroglioma.  Cancer. 2000;  88 862-869
  CrossrefPubMedGoogle Scholar
• 30 Robinson S, Cohen M, Prayson R, Ransohoff R, Tabrizi N, Miller R H. Constitutive expression of growth-related oncogene and its receptor in oligodendrogliomas.  Neurosurgery. 2001;  48 864-870
  PubMedGoogle Scholar
• 31 Russell D S, Rubinstein L J. Pathology of tumours of the nervous system. 4th edn. Edward Arnold, London 1977; 195-203
  Google Scholar
• 32 Schiffer D, Dutto A, Cavalla P, Bosone I, Chio A, Villano R, Bellotti C. Prognostic factors in oligodendroglioma.  Can J Neurol Sci. 1997;  24 313-319
  PubMedGoogle Scholar
• 33 Shaw E G, Scheithauer B W, O'Fallon J R, Tazelaar H D, Davis D H. Oligodendrogliomas: the Mayo Clinic experience.  J Neurosurg. 1992;  76 428-434
  PubMedGoogle Scholar
• 34 Smith J S, Wang X Y, Qian J, Haschk S M, Scheithauer B W, Jenkins R, James C D. Amplification of platelet derived growth factor receptor (PDG FRA)-gene occurs in oligodendrogliomas with grade IV anaplastic features.  J Neuropathol Exp Neurol. 2000;  59 495-503
  PubMedGoogle Scholar
• 35 Stupp R, Dietrich P Y, Ostermann-Kraljevic S. et al . Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide.  J Clin Oncol. 2002;  20 1375-1382
  CrossrefPubMedGoogle Scholar
• 36 Sun E M, Genka S, Shitare N. et al . Factors possibly influencing the prognosis of oligodendroglioma.  Neurosurgery. 1988;  22 886-891
  PubMedGoogle Scholar
• 37 Van der Bent M J, Looijenga L H, Longberger K. Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features.  Cancer. 2003;  97 1276-1284
  CrossrefPubMedGoogle Scholar
• 38 Vaquero J, Zurita M, Coca S, Oya S, Morales C. Prognostic significance of clinical and angiogenesis-related factors in low-grade oligodendrogliomas.  Surg Neurol. 2000;  54 229-234
  CrossrefPubMedGoogle Scholar
• 39 Warthon S B, Hamilton F A, Chan W K, Chan K K, Anderson J R. Proliferation and cell death in oligodendrogliomas.  Neuropathol Appl Neurobiol. 1998;  24 21-28
  PubMedGoogle Scholar
• 40 Westergaard L, Gjerris F, Klinken L. Prognostic factors in oligodendroglioma.  Acta Neurochir. 1997;  139 600-605
  CrossrefPubMedGoogle Scholar
• 41 Yeh S A, Lee T C, Chen H J, Lui C C, Sun L M, Wang C J, Huang E Y. Treatment outcomes and prognostic factors of patients with supratentorial low-grade oligodendroglioma.  Int J Radiat Oncol Biol Phys. 2002;  54 1405-1409
  CrossrefPubMedGoogle Scholar
• 42 Zulch K J. Brain Tumors: Their Biology and Pathology. 3rd edn. Springer, Berlin, Heidelberg 1986; 241
  Google Scholar

Prof. F. Maiuri

Dipartimento di Scienze Neurologiche · Cattedra di Neurochirurgia · Università “Federico II”

Via Pansini 5

80131 Napoli

Italy

Phone: +39/0 81/7 46 25 81

Phone: +39/0 81/7 46 25 94

Email: frmaiuri@unina.it