PMID- 23314677
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20240318
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 71
IP  - 3
DP  - 2013 Mar
TI  - Concomitant high gene copy number and protein overexpression of IGF1R and EGFR 
      negatively affect disease-free survival of surgically resected 
      non-small-cell-lung cancer patients.
PG  - 671-80
LID - 10.1007/s00280-012-2056-y [doi]
AB  - BACKGROUND: Insulin-like growth factor 1 receptor (IGF1R) represents a novel 
      molecular target in non-small-cell-lung cancer (NSCLC). IGF1R and epidermal 
      growth factor receptor (EGFR) activation are essential to mediate tumor cell 
      survival, proliferation, and invasion. This study investigates the prognostic 
      role of IGF1R and EGFR in surgically resected NSCLC. MATERIALS AND METHODS: IGF1R 
      and EGFR copy number gain (CNG) were tested by fluorescence in situ hybridization 
      (FISH) and protein expression by immunohistochemistry (IHC) in 125 stage 
      I-II-IIIA NSCLC patients. RESULTS: Fourty-six tumors (40.3%) were IGF1R 
      FISH-positive (FISH+), and 76 (67.2%) were EGFR FISH+. Tumors with concomitant 
      IGF1R/EGFR FISH+ were observed in 34 cases (30.1%). IGF1R and EGFR FISH+ were 
      associated with SCC histology (p = 0.01 and p = 0.04, respectively). IGF1R and 
      EGFR protein over-expression (IHC+) were detected in 45 (36.0%) and 69 (55.2%) 
      cases, respectively. Tumors with concomitant IGF1R/EGFR IHC+ were detected in 31 
      (24.8%) patients. IGF1R/EGFR FISH+ and IGF1R/EGFR IHC+ were significantly 
      associated (chi(2) = 4.02, p = 0.04). Patients with IGF1R/EGFR FISH+ and IGF1R/EGFR 
      IHC+ were associated with shorter disease-free survival (DFS) (p = 0.05 and p = 
      0.05, respectively). Patients with concomitant IGF1R/EGFR FISH+/IHC+ had a worse 
      DFS and overall survival (p = 0.005 and p = 0.01, respectively). The multivariate 
      model confirmed that IGF1R/EGFR FISH+/IHC+ (hazard ratio (HR), 4.08; p = 0.01) 
      and tumor stage (II-III vs I) (HR, 4.77; p = 0.003) were significantly associated 
      with worse DFS. CONCLUSIONS: IGF1R/EGFR FISH+ correlates with IGF1R/EGFR IHC+. 
      IGF1R/EGFR FISH+/IHC+ is an independent negative prognostic factor for DFS in 
      early NSCLC. These features may have important implications for future anti-IGF1R 
      therapeutic approaches.
FAU - Ludovini, V
AU  - Ludovini V
AD  - Department of Medical Oncology, S. Maria Della Misericordia Hospital, 1, G. 
      Dottori Street, 06132 Perugia, Italy. ludoviniv@hotmail.com
FAU - Flacco, A
AU  - Flacco A
FAU - Bianconi, F
AU  - Bianconi F
FAU - Ragusa, M
AU  - Ragusa M
FAU - Vannucci, J
AU  - Vannucci J
FAU - Bellezza, G
AU  - Bellezza G
FAU - Chiari, R
AU  - Chiari R
FAU - Minotti, V
AU  - Minotti V
FAU - Pistola, L
AU  - Pistola L
FAU - Tofanetti, F R
AU  - Tofanetti FR
FAU - Siggillino, A
AU  - Siggillino A
FAU - Baldelli, E
AU  - Baldelli E
FAU - Sidoni, A
AU  - Sidoni A
FAU - Daddi, N
AU  - Daddi N
FAU - Puma, F
AU  - Puma F
FAU - Varella-Garcia, M
AU  - Varella-Garcia M
FAU - Crino, L
AU  - Crino L
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130112
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology/*surgery
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - ErbB Receptors/*biosynthesis/*genetics
MH  - Female
MH  - Gene Dosage
MH  - Gene Expression/physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*genetics/*surgery
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Receptor, IGF Type 1/*biosynthesis/*genetics
MH  - Sex Factors
MH  - Smoking/adverse effects
PMC - PMC3963139
MID - NIHMS534932
COIS- Conflict of interest: The author(s) indicated no potential conflicts of interest.
EDAT- 2013/01/15 06:00
MHDA- 2013/04/09 06:00
PMCR- 2014/03/24
CRDT- 2013/01/15 06:00
PHST- 2012/09/17 00:00 [received]
PHST- 2012/12/12 00:00 [accepted]
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
PHST- 2014/03/24 00:00 [pmc-release]
AID - 10.1007/s00280-012-2056-y [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2013 Mar;71(3):671-80. doi: 
      10.1007/s00280-012-2056-y. Epub 2013 Jan 12.