PMID- 16258523
OWN - NLM
STAT- MEDLINE
DCOM- 20060328
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 86
IP  - 1
DP  - 2006 Jan
TI  - Amplifications of the epidermal growth factor receptor gene (egfr) are common in 
      phyllodes tumors of the breast and are associated with tumor progression.
PG  - 54-61
AB  - Phyllodes tumors of the breast are rare biphasic tumors with the potential for 
      invasion and metastatic spread. An important role of the epidermal growth factor 
      receptor (EGFR) in phyllodes tumors has been proposed. However, detailed 
      pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of 
      the breast (40 benign, 10 borderline and eight malignant) by means of egfr 
      fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory 
      sequence within intron 1 of egfr. Immunohistochemical staining was performed for 
      EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. 
      Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all 
      malignant tumors) in stromal tumor cells but not in the epithelial component. 
      Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and 
      intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes 
      tumors. Significant correlations were seen between tumor grade on the one hand 
      and EGFR overexpression (P=0.001) and intron 1 amplifications (P<0.05) on the 
      other. EGFR overexpression further correlated positively with immunohistochemical 
      staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 
      amplifications correlated with p16 (P<0.01), p21 (P=0.009) and p53 
      immunoreactivity (P<0.001). Neither EGFR overexpression nor whole-gene 
      amplification was observed in a control series of 167 fibroadenomas and only one 
      of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, 
      our results show for the first time that activating mutations in and 
      overexpression of egfr are associated with the progression in grade of phyllodes 
      tumors of the breast. The observed association between intron 1 amplification and 
      overexpression of EGFR provides further insight into regulation mechanisms of 
      EGFR overexpression.
FAU - Kersting, Christian
AU  - Kersting C
AD  - Institute of Pathology, University of Muenster, Muenster, Germany.
FAU - Kuijper, Arno
AU  - Kuijper A
FAU - Schmidt, Hartmut
AU  - Schmidt H
FAU - Packeisen, Jens
AU  - Packeisen J
FAU - Liedtke, Cornelia
AU  - Liedtke C
FAU - Tidow, Nicola
AU  - Tidow N
FAU - Gustmann, Christian
AU  - Gustmann C
FAU - Hinrichs, Bernd
AU  - Hinrichs B
FAU - Wulfing, Pia
AU  - Wulfing P
FAU - Tio, Joke
AU  - Tio J
FAU - Boecker, Werner
AU  - Boecker W
FAU - van Diest, Paul
AU  - van Diest P
FAU - Brandt, Burkhard
AU  - Brandt B
FAU - Buerger, Horst
AU  - Buerger H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (DNA Primers)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Base Sequence
MH  - Breast Neoplasms/*genetics/pathology
MH  - DNA Primers
MH  - Disease Progression
MH  - ErbB Receptors/*genetics
MH  - *Gene Amplification
MH  - Gene Dosage
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Phyllodes Tumor/*genetics/pathology
EDAT- 2005/11/01 09:00
MHDA- 2006/03/29 09:00
CRDT- 2005/11/01 09:00
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2006/03/29 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
AID - S0023-6837(22)03293-7 [pii]
AID - 10.1038/labinvest.3700358 [doi]
PST - ppublish
SO  - Lab Invest. 2006 Jan;86(1):54-61. doi: 10.1038/labinvest.3700358.