PMID- 20381121
OWN - NLM
STAT- MEDLINE
DCOM- 20100729
LR  - 20181201
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 41
IP  - 8
DP  - 2010 Aug
TI  - EGFR fluorescence in situ hybridization-positive lung adenocarcinoma: incidence 
      of coexisting KRAS and BRAF mutations.
PG  - 1053-60
LID - 10.1016/j.humpath.2010.01.008 [doi]
AB  - Despite growing evidence that epidermal growth factor receptor (EGFR) and 
      v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation analysis is 
      the most reliable predictor of the lung carcinoma response to EGFR-targeted 
      therapies, there is still discussion about the role of EGFR fluorescence in situ 
      hybridization (FISH). Studies focusing on EGFR FISH as a predictor of response to 
      EGFR-targeted therapies mostly focused on the relationship between EGFR FISH and 
      EGFR mutations. The incidence of KRAS and V-raf murine sarcoma viral oncogene 
      homolog B1 (BRAF) mutations in EGFR-amplified or EGFR FISH-positive lung 
      adenocarcinomas remains unknown. The aim of this study was to prospectively 
      characterize the incidence of KRAS and BRAF mutations in EGFR FISH-positive 
      surgically treated lung adenocarcinomas. Of 386 primary lung adenocarcinomas, 77 
      (20%) were EGFR FISH positive by University of Colorado criteria. The incidence 
      of KRAS mutations in EGFR FISH-positive lung adenocarcinomas was 23% and was not 
      significantly different from the incidence of KRAS mutations in EGFR 
      FISH-negative subsets of adenocarcinoma (32%). A higher mean ratio between EGFR 
      and chromosome 7 enumeration probe (EGFR/CEP7) was observed in EGFR-mutated 
      tumors when compared to cases with KRAS mutation (13 versus 4.5, respectively). 
      Our results showed significant number of EGFR FISH positive/amplified lung 
      adenocarcinomas harboring KRAS mutation. It appears that an increase in EGFR/CEP7 
      ratio to cutoff point of 4.5 may distinguish between coexisting EGFR (FISH ratio 
      of >5) or KRAS (FISH ratio of 2 to 5) mutations. Observations presented here 
      indicate that the patient selection for EGFR-targeted therapies should include 
      EGFR and KRAS mutational analysis, probably complemented by EGFR FISH studies.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Chiosea, Simion
AU  - Chiosea S
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. 
      chioseasi@upmc.edu
FAU - Shuai, Yongli
AU  - Shuai Y
FAU - Cieply, Kathleen
AU  - Cieply K
FAU - Nikiforova, Marina N
AU  - Nikiforova MN
FAU - Dacic, Sanja
AU  - Dacic S
LA  - eng
PT  - Journal Article
DEP - 20100408
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics
MH  - Chromosomes, Human, Pair 7/genetics/ultrastructure
MH  - ErbB Receptors/antagonists & inhibitors/*genetics
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Polyribosomes/genetics
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - ras Proteins/*genetics
EDAT- 2010/04/13 06:00
MHDA- 2010/07/30 06:00
CRDT- 2010/04/13 06:00
PHST- 2009/10/28 00:00 [received]
PHST- 2010/01/04 00:00 [revised]
PHST- 2010/01/08 00:00 [accepted]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2010/07/30 06:00 [medline]
AID - S0046-8177(10)00024-9 [pii]
AID - 10.1016/j.humpath.2010.01.008 [doi]
PST - ppublish
SO  - Hum Pathol. 2010 Aug;41(8):1053-60. doi: 10.1016/j.humpath.2010.01.008. Epub 2010 
      Apr 8.