PMID- 25025175
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - The three receptor tyrosine kinases c-KIT, VEGFR2 and PDGFRalpha, closely spaced at 
      4q12, show increased protein expression in triple-negative breast cancer.
PG  - e102176
LID - 10.1371/journal.pone.0102176 [doi]
LID - e102176
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of 
      breast cancer with poor prognosis and no targeted therapy available. Receptor 
      tyrosine kinases (RTKs) are emerging targets in anticancer therapy and many 
      RTK-inhibiting drugs are currently being developed. The aim of this study was to 
      elucidate if there is a correlation between the protein expression of three RTKs 
      c-KIT, VEGFR2 and PDGFRalpha, their gene copy number, and prognosis in TNBC compared 
      to non-TNBC. METHODS: Tumor tissue samples from patients diagnosed with primary 
      breast cancer were stained with immunohistochemistry (IHC) for protein 
      assessment, and with fluorescence in situ hybridization (FISH) for gene copy 
      number determination. Breast cancer mortality (BCM), measured from the date of 
      surgery to death, was used as endpoint. RESULTS: The cohort included 464 
      patients, out of which 34 (7.3%) had a TNBC. High expression of the three RTKs 
      was more common in TNBC compared to non-TNBC: c-KIT 49% vs. 10% (P<0.001), PDGFRalpha 
      32% vs. 19% (P = 0.07) and VEGFR2 32% vs. 6% (P<0.001). The odds ratio (OR) of 
      c-KIT, VEGFR2 and PDGFRalpha positivity, adjusted for tumor characteristics, was 6.8, 
      3.6 and 1.3 times higher for TNBC than for non-TNBC. 73.5% of the TNBC had high 
      expression of at least one of the three investigated receptors, compared to 30.0% 
      of the non-TNBC (P<0.001). Survival analysis showed no significant difference in 
      BCM for TNBC patients with high vs. low c-KIT, PDGFRalpha or VEGFR2 protein 
      expression. 193 (42%) tumors were evaluated with FISH. No correlation was seen 
      between increased gene copy number and TNBC, or between increased gene copy 
      number and high protein expression of the RTK. CONCLUSION: c-KIT, VEGFR2 and 
      PDGFRalpha show higher protein expression in TNBC compared to non-TNBC. Further 
      investigation clarifying the importance of these RTKs in TNBC is encouraged, as 
      they are possible targets for anticancer therapy.
FAU - Jansson, Sara
AU  - Jansson S
AD  - Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund 
      University, Lund, Sweden.
FAU - Bendahl, Par-Ola
AU  - Bendahl PO
AD  - Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund 
      University, Lund, Sweden.
FAU - Grabau, Dorthe Aamand
AU  - Grabau DA
AD  - Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund 
      University, Lund, Sweden.
FAU - Falck, Anna-Karin
AU  - Falck AK
AD  - Department of Surgery, Hospital of Helsingborg, Helsingborg, Sweden.
FAU - Ferno, Marten
AU  - Ferno M
AD  - Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund 
      University, Lund, Sweden.
FAU - Aaltonen, Kristina
AU  - Aaltonen K
AD  - Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund 
      University, Lund, Sweden.
FAU - Ryden, Lisa
AU  - Ryden L
AD  - Division of Surgery, Department of Clinical Sciences Lund, Skane University 
      Hospital, Lund, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140715
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosomes, Human, Pair 4
MH  - Female
MH  - Gene Dosage
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-kit/genetics/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics/*metabolism
MH  - Triple Negative Breast Neoplasms/genetics/*metabolism/mortality/pathology
MH  - Tumor Burden
MH  - Vascular Endothelial Growth Factor Receptor-2/genetics/*metabolism
PMC - PMC4098911
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/07/16 06:00
MHDA- 2015/03/31 06:00
PMCR- 2014/07/15
CRDT- 2014/07/16 06:00
PHST- 2014/01/08 00:00 [received]
PHST- 2014/06/17 00:00 [accepted]
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2014/07/15 00:00 [pmc-release]
AID - PONE-D-14-01046 [pii]
AID - 10.1371/journal.pone.0102176 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 15;9(7):e102176. doi: 10.1371/journal.pone.0102176. 
      eCollection 2014.