PMID- 21445634
OWN - NLM
STAT- MEDLINE
DCOM- 20110627
LR  - 20231213
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 458
IP  - 5
DP  - 2011 May
TI  - Involvement of HER-2/neu and metastasis-related proteins in the development of 
      ileal neuroendocrine tumors.
PG  - 525-36
LID - 10.1007/s00428-011-1069-y [doi]
AB  - HER-2/neu overexpression and/or gene amplification occurs in several human 
      malignancies, frequently correlates with tumor aggressiveness, and provides the 
      basis for treatment with trastuzumab. Among neuroendocrine neoplasms (NEN) of the 
      gastroenteropancreatic (GEP) tract, ileal neuroendocrine tumors show peculiar 
      features of malignancy with frequent metastases at the diagnosis. We investigated 
      the overexpression and/or amplification of HER-2/neu and the involvement of the 
      metastasis-related proteins c-Met, MTA-1, and VEGF in 24 primary ileal NEN by 
      immunohistochemistry and fluorescence in situ hybridization (FISH). Data were 
      compared with those of 43 GEP endocrine tumors of other sites. All primary ileal 
      NEN showed an intense membranous and cytoplasmic immunostaining for HER-2/neu. 
      According to the breast cancer scoring system, 17% of ileal carcinoids showed a 
      score of 3+ and 71% with a score of 2+ with a significant difference respect the 
      non-ileal GEP endocrine tumors (p < 0.0000). FISH analysis revealed chromosome 17 
      polysomy in 33% of 2+/3+ ileal tumors but not HER-2/neu gene amplification. The 
      c-Met and MTA-1 but not VEGF were overexpressed in almost all ileal NEN, whereas 
      VEGF presented more frequently a normal staining. The comparisons with the other 
      GEP NEN demonstrated significant differences for all the three proteins 
      (p < 0.0000, p < 0.0002, and p < 0.001, respectively). These findings suggest 
      that in ileal NEN, HER-2/neu overexpression plays a role in the carcinogenetic 
      process and by triggering the altered expression of c-Met and MTA-1, may activate 
      the molecular pathway(s) promoting tumor progression and metastasis development. 
      Ileal HER-2/neu overexpressing neuroendrocrine tumors may constitute potential 
      candidates for target therapy with specific humanized monoclonal antibodies.
FAU - Azzoni, Cinzia
AU  - Azzoni C
AD  - Department of Pathology, Section of Anatomic Pathology, University of Parma, 
      Parma, Italy. cinzia.azzoni@unipr.it
FAU - Bottarelli, Lorena
AU  - Bottarelli L
FAU - Cecchini, Stefano
AU  - Cecchini S
FAU - Lagrasta, Costanza
AU  - Lagrasta C
FAU - Pizzi, Silvia
AU  - Pizzi S
FAU - D'Adda, Tiziana
AU  - D'Adda T
FAU - Tamburini, Elisa
AU  - Tamburini E
FAU - Rindi, Guido
AU  - Rindi G
FAU - Bordi, Cesare
AU  - Bordi C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110329
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (MTA1 protein, human)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Antibodies, Monoclonal, Humanized
MH  - Gene Amplification
MH  - Genes, erbB-2
MH  - Histone Deacetylases/*physiology
MH  - Humans
MH  - Ileal Neoplasms/*genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Neuroendocrine Tumors/*genetics
MH  - Proto-Oncogene Proteins c-met/*physiology
MH  - Receptor, ErbB-2/*genetics
MH  - Repressor Proteins/*physiology
MH  - Trans-Activators
MH  - Trastuzumab
MH  - Vascular Endothelial Growth Factor A/physiology
EDAT- 2011/03/30 06:00
MHDA- 2011/06/28 06:00
CRDT- 2011/03/30 06:00
PHST- 2010/12/07 00:00 [received]
PHST- 2011/03/17 00:00 [accepted]
PHST- 2011/03/14 00:00 [revised]
PHST- 2011/03/30 06:00 [entrez]
PHST- 2011/03/30 06:00 [pubmed]
PHST- 2011/06/28 06:00 [medline]
AID - 10.1007/s00428-011-1069-y [doi]
PST - ppublish
SO  - Virchows Arch. 2011 May;458(5):525-36. doi: 10.1007/s00428-011-1069-y. Epub 2011 
      Mar 29.