Loss of 1p, 19q, and 10q heterozygosity prospectively predicts prognosis of oligodendroglial tumors--towards individualized tumor treatment?

The purpose of this study was to determine whether chromosome 10q loss is a predictor of tumor aggressiveness and poor clinical outcome in patients with oligodendroglial tumors alone or together with loss of heterozygosity (LOH) on chromosomes 1p and 19q. A microsatellite analysis was performed on sections from 130 patients with grade II and grade III oligodendroglial tumors to assess the allelic status of chromosomes 1p, 19q, and 10q, plus detailed clinical and radiological information was taken prospectively. Median age at diagnosis was 45.5 years. Seventy-eight patients had disease progression after initial therapy; median progression-free survival (PFS) was 27.5 months. Age <47 years, postoperative Karnofsky performance score >65, no contrast enhancement on MRI, grade II, and complete removal on surgery were significantly correlated with a better PFS. Median overall survival (OS) was 40.5 months. Pure oligodendroglioma and temozolomide chemotherapy were correlated with better OS. 10q LOH was correlated with anaplastic grade and 1p19q LOH correlated with pure oligodendroglioma. There was a significant association between LOH status and the tumors' response to chemotherapy: 92.3% with 1p19q LOH, 83.3% without allelic losses, 50% with 1p19q10q LOH, and 14.5% with 10q LOH. Patients with 10q LOH alone had PFS of 6 months and a 3-year survival rate of 1%, when compared with 36 months and 85%, respectively, in patients with 1p19q LOH but without 10q LOH. 1p loss was correlated with better PFS (P < .005) and OS (P = .0007), whereas 10q loss was correlated with decreased PFS (P < .0001) and OS (P < .0001). 10q LOH predicted a survival disadvantage in patients with oligodendroglial tumors irrespective of 1p/19q LOH status.

[1]  D K Pearl,et al.  Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas , 1997, Cancer.

[2]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[3]  Charles Duyckaerts,et al.  The 2007 WHO classification of tumors of the central nervous system – what has changed? , 2008, Current opinion in neurology.

[4]  C. Daumas-Duport,et al.  Gliomes : classifications de l'OMS et de l'Hôpital Sainte-Anne , 2000 .

[5]  C. Daumas-Duport,et al.  [Gliomas: WHO and Sainte-Anne Hospital classifications]. , 2000, Annales de pathologie.

[6]  D. Horsman,et al.  Loss of Heterozygosity for Loci on Chromosome Arms 1p and 10q in Oligodendroglial Tumors: Relationship to Outcome and Chemosensitivity , 2003, Journal of Neuro-Oncology.

[7]  D. Louis,et al.  Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. , 1998, Journal of the National Cancer Institute.

[8]  S. Brem,et al.  Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973-1991. , 1998, Journal of neurosurgery.

[9]  Y. Marie,et al.  Prognostic stratification of patients with anaplastic gliomas according to genetic profile , 2006, Cancer.

[10]  Walter Curran,et al.  Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Denis Lacombe,et al.  Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Mitsutoshi Nakamura,et al.  Genetic analysis to complement histopathological diagnosis of brain tumors. , 2007, Histology and histopathology.

[13]  S. Faivre Tumeurs du système nerveux central , 1999 .

[14]  G. Fuller,et al.  Toward a molecular classification of the gliomas: histopathology, molecular genetics, and gene expression profiling. , 2000, Histology and histopathology.

[15]  Madan Arora,et al.  Primary brain tumors in adults. , 2008, American family physician.

[16]  R A Betensky,et al.  Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  Faith Davis,et al.  Brain tumor survival: Results from the National Cancer Data Base , 1998, Journal of Neuro-Oncology.

[18]  Wei Zhang,et al.  Molecular Classification of Human Diffuse Gliomas by Multidimensional Scaling Analysis of Gene Expression Profiles Parallels Morphology‐Based Classification, Correlates with Survival, and Reveals Clinically‐Relevant Novel Glioma Subsets , 2002, Brain pathology.

[19]  G S Bauman,et al.  Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas. , 2000, International journal of radiation oncology, biology, physics.

[20]  G. Broggi,et al.  Association of chromosome 10 losses and negative prognosis in oligoastrocytomas , 2002, Annals of neurology.

[21]  K. Hoang-Xuan,et al.  Analysis of loss of chromosome 10q, DMBT1 homozygous deletions, and PTEN mutations in oligodendrogliomas. , 2002, Journal of neurosurgery.

[22]  B. Scheithauer,et al.  Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  D. Louis,et al.  Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome 1p loss. , 2000, Journal of neurosurgery.

[24]  R A Betensky,et al.  Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. , 2001, Cancer research.

[25]  P. Kleihues,et al.  Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. , 2005, Journal of neuropathology and experimental neurology.

[26]  K. Mokhtari,et al.  Tumeurs du système nerveux central. Classifications histologiques et topographiques, épidémiologie , 2011 .

[27]  D. Louis WHO classification of tumours of the central nervous system , 2007 .

[28]  T. Golub,et al.  Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. , 2003, Cancer research.

[29]  K. Hoang-Xuan,et al.  Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression , 2001, Neurology.

[30]  K. Hoang-Xuan,et al.  Primary brain tumours in adults , 2003, The Lancet.

[31]  A. Poustka,et al.  Comprehensive Allelotype and Genetic Analysis of 466 Human Nervous System Tumors , 2000, Journal of neuropathology and experimental neurology.