PMID- 26555375
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 11
DP  - 2015
TI  - FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell 
      Carcinoma Subtype in Esophageal Carcinoma.
PG  - e0141867
LID - 10.1371/journal.pone.0141867 [doi]
LID - e0141867
AB  - BACKGROUND AND AIMS: Amplification of the fibroblast growth factor receptor 1 
      (FGFR1) is believed to predict response to multi-kinase inhibitors targeting 
      FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted 
      therapies are highly warranted. METHODS: This study was designed to investigate 
      the prevalence and clinical significance of FGFR1 amplification in a tissue 
      microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the 
      esophagus, using dual-labeling fluorescence in situ hybridization (FISH) 
      analysis. RESULTS: FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 
      copy numbers >/= 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 
      202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There 
      was no association between FGFR1 amplification and tumor phenotype or clinical 
      outcome. To study potential heterogeneity of FGFR1 amplification, all available 
      tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large 
      sections. This analysis revealed complete homogeneity of FGFR1 amplification in 
      20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, 
      FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 
      patients with FGFR1 amplified primary cancers. CONCLUSIONS: In conclusion, FGFR1 
      amplification occurs in a relevant subgroup of carcinomas of the esophagus and 
      may play a particular role for development of squamous cell cancers. The high 
      homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified 
      esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt 
      for clinical studies in this tumor type.
FAU - von Loga, Katharina
AU  - von Loga K
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Kohlhaussen, Jule
AU  - Kohlhaussen J
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Burkhardt, Lia
AU  - Burkhardt L
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Simon, Ronald
AU  - Simon R
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Steurer, Stefan
AU  - Steurer S
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Burdak-Rothkamm, Susanne
AU  - Burdak-Rothkamm S
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Jacobsen, Frank
AU  - Jacobsen F
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Sauter, Guido
AU  - Sauter G
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Krech, Till
AU  - Krech T
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20151110
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.7.10.1 (FGFR1 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
SB  - IM
MH  - Adenocarcinoma/*genetics/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/*genetics/pathology
MH  - Esophageal Neoplasms/*genetics/pathology
MH  - Female
MH  - Gene Amplification/*physiology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Receptor, Fibroblast Growth Factor, Type 1/*genetics
PMC - PMC4640518
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/11/12 06:00
MHDA- 2016/06/15 06:00
PMCR- 2015/11/10
CRDT- 2015/11/12 06:00
PHST- 2015/07/23 00:00 [received]
PHST- 2015/10/14 00:00 [accepted]
PHST- 2015/11/12 06:00 [entrez]
PHST- 2015/11/12 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
PHST- 2015/11/10 00:00 [pmc-release]
AID - PONE-D-15-30098 [pii]
AID - 10.1371/journal.pone.0141867 [doi]
PST - epublish
SO  - PLoS One. 2015 Nov 10;10(11):e0141867. doi: 10.1371/journal.pone.0141867. 
      eCollection 2015.