PMID- 22472960
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20220817
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 36
IP  - 8
DP  - 2012 Aug
TI  - Paradoxical relationship between the degree of EGFR amplification and outcome in 
      glioblastomas.
PG  - 1186-93
LID - 10.1097/PAS.0b013e3182518e12 [doi]
AB  - Glioblastoma (GBM) is the most common primary brain tumor in adults and often has 
      amplification of the epidermal growth factor receptor (EGFR) gene. The value of 
      EGFR as a prognostic marker in GBMs is unclear; some studies have shown an 
      adverse correlation, whereas others have indicated a neutral or even favorable 
      association with longer survival. Furthermore, EGFR-amplified GBMs are usually 
      regarded as a single subgroup of tumors, although the range of EGFR copy number 
      varies greatly. In this study, 532 GBMs were analyzed for EGFR amplification via 
      fluorescence in situ hybridization at the time of initial diagnosis. Although 
      there was no difference in survival by EGFR amplification (P = 0.33), 
      stratification by the amount of EGFR amplification showed that, surprisingly, 
      median survival was 39% longer in the high-amplifier group (EGFR:chromosome 7 
      ratio >20) compared to nonamplified GBMs (P = 0.03) and was 43% longer compared 
      to GBMs with low to moderate EGFR amplification (EGFR:chromosome 7 ratio = 2 to 
      20; P = 0.0007). Stratifying by postsurgical treatment regimens, this difference 
      was seen only when temozolomide (TMZ) was used; tumors without amplification and 
      with high EGFR amplification both responded better to TMZ than those with low to 
      moderate amplification (P = 0.01), whereas GBMs that had not been treated with 
      adjuvant therapy nor with adjuvant therapy lacking TMZ showed no survival 
      differences (P = 0.63 and 0.91, respectively). These results suggest that GBMs 
      with EGFR amplification are a heterogenous group of tumors and that behavior 
      might differ according to the degree of amplification, although not in a 
      straightforward dose-response manner.
FAU - Hobbs, Jonathan
AU  - Hobbs J
AD  - Department of Pathology, University of Kentucky, Lexington, KY 40536, USA.
FAU - Nikiforova, Marina N
AU  - Nikiforova MN
FAU - Fardo, David W
AU  - Fardo DW
FAU - Bortoluzzi, Stephanie
AU  - Bortoluzzi S
FAU - Cieply, Kathleen
AU  - Cieply K
FAU - Hamilton, Ronald L
AU  - Hamilton RL
FAU - Horbinski, Craig
AU  - Horbinski C
LA  - eng
GR  - K08 CA155764/CA/NCI NIH HHS/United States
GR  - K08 CA155764-01A1/CA/NCI NIH HHS/United States
GR  - K08CA155764-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/therapeutic use
MH  - Biomarkers, Tumor/genetics
MH  - Brain Neoplasms/*genetics/*mortality/pathology
MH  - Dacarbazine/analogs & derivatives/therapeutic use
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Gene Amplification
MH  - Genes, erbB-1/*genetics
MH  - Glioblastoma/*genetics/*mortality/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Temozolomide
MH  - Young Adult
PMC - PMC3393818
MID - NIHMS366191
EDAT- 2012/04/05 06:00
MHDA- 2012/09/19 06:00
PMCR- 2013/08/01
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - 10.1097/PAS.0b013e3182518e12 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2012 Aug;36(8):1186-93. doi: 10.1097/PAS.0b013e3182518e12.