title: Case comparison and literature review of glioblastoma: A tale of two tumors.
abstract: BACKGROUND
  Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous group of tumors. We describe two cases with histopathologically and molecularly similar tumors, but very different outcomes. We attempt to illustrate the need for improved prognostic markers for GBM.
  
  
  METHODS
  Two patients with similar molecular profiles were retrospectively identified. The following markers were assessed: O (6)-methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status. Each patient was assigned a Karnofsky performance score at presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation, 28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The patient underwent resection followed by radiation therapy and 2 years of chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor eventually recurred and the patient expired 72 months after initial diagnosis. Case 2 (63-year-old male) was a right frontal white matter mass consistent with glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2 mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status inconclusive. A radical subtotal resection was performed; however, 2 weeks later symptoms had returned. Subsequent imaging revealed a tumor larger than at diagnosis. The patient expired 3 months after initial diagnosis.
  
  
  CONCLUSIONS
  The need for formulating more robust means to classify GBM tumor subtypes is paramount. Standard histopathologic and molecular analyses are costly and did not provide either of these patients with a realistic appraisal of their prognosis. Individualized whole genome testing similar to that being reported for medulloblastoma and other tumors may be preferable to the array of tests as currently utilized.
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mendez
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Alp
authors.initials: A
authors.lastname: Ozpinar
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Raskin
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Sakir H
authors.initials: SH
authors.lastname: Gultekin
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA ; Section of Neurological Surgery, Operative Care Division, Portland Veterans Administration Hospital, Portland, OR, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Ross
keywords: 1p/19q deletion; O6-methylguanine DNA methyltransferase methylation and expression; epidermal growth factor receptor amplification; glioblastoma; isocitrate dehydrogenase1; isocitrate dehydrogenase1 mutation; phosphatase and tensin homolog deletion; prognosis