title: Molecular markers in low-grade gliomas: predictive or prognostic?
abstract: OBJECTIVE
  To investigate whether TP53 mutation, 1p/19q codeletions, O(6)-methylguanylmethyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation predict natural course of disease or response to radiotherapy or chemotherapy or both in low-grade glioma patients.
  
  
  METHODS
  Cohort A consisted of 89 patients with diffuse astrocytoma World Health Organization (WHO) grade II (n = 40), oligoastrocytoma (n = 23), or oligodendroglioma (n = 26) who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression [progressive disease (PD); n = 59] and beyond or until the end of follow-up (n = 30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analyzed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations.
  
  
  RESULTS
  Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI: 3.1-5.1). No molecular marker was prognostic for PFS after surgery alone, using multivariate adjustment for histology, age, and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in oligoastrocytomas (OA II)/oligodendrogliomas (O II) and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B.
  
  
  CONCLUSIONS
  None of the parameters are sensitive prognostic biomarkers in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favorable outcome, the nonrandomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS.
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Center & Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University Heidelberg, Heidelberg, Germany. christian.hartmann@med.uni-heidelberg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Hentschel
authors.forename: Marcos
authors.initials: M
authors.lastname: Tatagiba
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Clemens
authors.initials: C
authors.lastname: Seidel
authors.forename: Robert
authors.initials: R
authors.lastname: Stein
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor