PMID- 21587084
OWN - NLM
STAT- MEDLINE
DCOM- 20111215
LR  - 20220316
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 6
IP  - 8
DP  - 2011 Aug
TI  - Higher dosage of the epidermal growth factor receptor mutant allele in lung 
      adenocarcinoma correlates with younger age, stage IV at presentation, and poorer 
      survival.
PG  - 1407-12
LID - 10.1097/JTO.0b013e31821d41af [doi]
AB  - INTRODUCTION: The clinical significance of epidermal growth factor receptor 
      (EGFR) mutant allele specific imbalance (MASI) in lung adenocarcinomas is 
      unknown. METHODS: EGFR MASI was characterized by sequencing electropherograms 
      (SEs) and EGFR fluorescence in situ hybridization (FISH) in 96 prospectively 
      tested lung adenocarcinoma patients with a median follow-up of 20 months (all 
      cases were EGFR mutation-positive). RESULTS: In 25 cases, the mutant allele (MA) 
      peak was higher than the wild-type allele (WA) peak, indicating the presence of 
      EGFR MASI (25/96, 26%). The adenocarcinomas with EGFR MASI had a 4.4-fold higher 
      average EGFR/Chromosome Enumeration Probe 7 ratio than carcinomas without MASI 
      (7.9 +/- 3.8 versus 1.8 +/- 0.6, p = 0.01). A high degree of correlation between the 
      MA/WA ratio (SE) and the EGFR/CEP7 ratio (FISH) (rho = 0.757, p = 0.003) validated 
      the quantitative nature of SE. Amplification was the most common mechanism of 
      EGFR MASI (13/21, 62%). EGFR MASI was more commonly associated with exon 19 
      mutations than with exon 21 mutations (19/53, 36%, versus 6/43, 14%, p = 0.015, 
      odds ratio [OR] = 3.4) and in patients younger than 65 years (17/46, 37%, versus 
      8/50, 16%, p = 0.019, OR = 3.1). Patients with EGFR MASI presented with stage IV 
      disease more frequently (p = 0.01, OR = 3.5) and had a poorer disease-specific 
      survival rate (p = 0.021, 54% versus 83% at 31 months). CONCLUSIONS: EGFR MASI in 
      lung adenocarcinomas can be assessed based on SE and can be used to identify 
      younger patients with more aggressive disease.
FAU - Oakley, Gerard J 3rd
AU  - Oakley GJ 3rd
AD  - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania, USA.
FAU - Chiosea, Simion I
AU  - Chiosea SI
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adenocarcinoma/genetics/mortality/pathology
MH  - Age Factors
MH  - Aged
MH  - Alleles
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*mortality/pathology
MH  - Cohort Studies
MH  - *DNA Copy Number Variations
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Neoplasm Staging
MH  - Polymerase Chain Reaction
MH  - Prospective Studies
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2011/05/19 06:00
MHDA- 2011/12/16 06:00
CRDT- 2011/05/19 06:00
PHST- 2011/05/19 06:00 [entrez]
PHST- 2011/05/19 06:00 [pubmed]
PHST- 2011/12/16 06:00 [medline]
AID - S1556-0864(15)31070-4 [pii]
AID - 10.1097/JTO.0b013e31821d41af [doi]
PST - ppublish
SO  - J Thorac Oncol. 2011 Aug;6(8):1407-12. doi: 10.1097/JTO.0b013e31821d41af.