Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation

Abstract

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with "glioblastoma multiforme." We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as "short-term" for TTP of less than 6 months (n = 54), and "long-term" for TTP of more than 12 months (n = 52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastoma multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only prognostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.

Ionizing radiation modulates vascular endothelial growth factor (VEGF) expression through multiple mitogen activated protein kinase dependent pathways

“…That radiation exposure enhanced expression of VEGF may have profound e ects on tumor cell biology. It is known that glioblastoma tumors are both highly metastatic and contain a large vascular network, in agreement with our observation of high VEGF promoter activity and protein levels (Kraus et al, 2000;Huhn et al, 1999;Barth, 1998). In addition, many of these tumors have been observed to proliferate, even during radiotherapy.…”

“…The primary therapeutic strategy in GBM is surgery followed by radiotherapy, however despite these interventions, such tumors frequently have a high morbidity, with 50% survival rates of less than 30 months (Kraus et al, 2000;Huhn et al, 1999). Several animal model systems have been used to examine GBM, including the Fisher 344 rat and the syngeneic cell lines T9 and RT2 (Barth, 1998).…”

Correlation of in vitro infiltration with glioma histological type in organotypic brain slices

“…Up to four times longer TTP was documented for 1p/19q codeleted Ols than for tumours without these deletions (Fallon et al, 2004). Likewise, in a series of pure GBMs and GOCs, 90% of the patients with unusually long TTP had tumours with an oligodendroglial component (Kraus et al, 2000). Besides the numbers of invading cells, TTP could be influenced by spatial patterns.…”

“…Similarly, in several studies gliomas with grade IV histology and an oligodendroglial component have been associated with better prognosis than pure GBMs (Donahue et al, 1997;Kraus et al, 2000). There is a seeming contradiction between this evidence and results of comparative studies which have invariably documented higher proliferation (Deckert et al, 1989;Karamitopoulou et al, 1994;Schiffer et al, 1995;Gordower et al, 1998;Heesters et al, 1999Heesters et al, , 2002Geiger et al, 2000) and lower apoptotic rates (Geiger et al, 2000;Heesters et al, 2002) for Ols than for As of similar grade.…”

The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation

“…33 The opposite picture is seen in tumours with astrocytic phenotype. -1p and/or -19q are only seen in a minority of GBMs (-1p 0-24%; -19q 0-33%; both 0-14%), 8,24,25,[34][35][36][37] and grade III AAs appear to be similar. 24,25,[36][37][38] In astrocytic tumours, -10q appears to increase with tumour grade: deletions are detected in approximately 35% of AAs, 8,37,[39][40][41][42] with incidence rising to around 75% in GBMs.…”