EXPRESSION OF HER-2 CORRELATED PROTEINS IN ILEAL CARCINOIDS Azzoni C., Giordano G., Bottarelli L.,...
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Transcript of EXPRESSION OF HER-2 CORRELATED PROTEINS IN ILEAL CARCINOIDS Azzoni C., Giordano G., Bottarelli L.,...
EXPRESSION OF HER-2 CORRELATED
PROTEINS IN ILEAL CARCINOIDS
Azzoni C., Giordano G., Bottarelli L., Tamburini E., D’Adda T., Pizzi S., Rindi G., Bordi C.
Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, Parma University,
Parma - Italy
BACKGROUNDBACKGROUNDIn a previous study of our laboratory we found a high HER-2/neu immunohistochemical expression in ileal midgut carcinoids (see data in Patients) at variance with other gastroenteropancreatic endocrine tumors
HER-2/neu overexpression may be involved in the carcinogenetic process of malignant ileal carcinoids
Involvement of metastasis-related proteins c-MET, Involvement of metastasis-related proteins c-MET, MTA-1 and VEGF activated by HER-2/MTA-1 and VEGF activated by HER-2/neuneu
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C-METC-MET
chromosome 7q31
tyrosine kinase receptor for Scatter Factor (also known as Hepatocyte Growth Factor)
stimulating cell proliferation, dissociation, motility, extracellular matrix invasion and metastatic behavior of a large array of neoplasms
overexpressed in several type of tumors, including thyroid, pancreatic, colorectal and breast carcinomas
in endocrine pancreatic tumors the expression of MET was found to be higher in tumors with metastases and worse prognosis
MTA-1MTA-1
chromosome 14q32
nuclear regulatory protein that interacts with specific genes involved in cellular regulation, invasion and progression
expression of MTA-1 gene was increased four-times in cerbB2/neu stable transfectants cells compared to untransfected cells
MTA-1 is overexpressed in a variety of human cancers including cancers of the breast, ovary, lung, gastrointestinal system and colorectum
VEGFVEGF chromosome 6p12
highly specific mitogen for vascular endothelial cells
clinical importance for tumor growth of solid malignancies in various organs including breast, lung, prostate and colon
preclinical and clinical findings support VEGF as a promising target for anticancer therapy
VEGF has been demonstrated to be highly expressed in midgut ileal carcinoids whereas it is focally expressed in other gastroenteropancreatic neuroendocrine tumors, suggesting the possible use of this protein as a serum marker for ileal carcinoid
EXPERIMENTAL DESIGNEXPERIMENTAL DESIGN
c-MET, MTA-1 and VEGF were examined by immunohistochemistry in 35 primary ileal carcinoids and in 5 metastatic tissues
We also determined the association of these proteins with the status of Her-2/neu expression
PATIENTSPATIENTSPRIMARY TUMORSPRIMARY TUMORS METASTASESMETASTASES
Legend: F, female; M, male; nd: not determined
METHODSMETHODSAntibodyAntibody CloneClone RetrievalRetrieval DilutionDilution IncubationIncubation PositivityPositivity
c-MET sc-161Santa Cruz,
Biotechology
EDTA ph 9 1:50 overnight membrane, cytoplasmic
MTA-1 Sc-17773Santa Cruz,
Biotechology
EDTA ph 9 1:50 overnight nuclear
VEGF Sc-7269Santa Cruz,
Biotechology
EDTA ph 9 1:100 overnight cytoplasmic
Semiquantitative analisysSemiquantitative analisys
intensity and positivity of immunohistochemical stainingintensity and positivity of immunohistochemical staining
c-MET, MTA-1, VEGF : 4-point scale:
0: no staining, 1: mild staining, 2: moderate staining, 3: intense staining
MTA-1c-MET
VEGF
Intense staining of Intense staining of metastasis- related metastasis- related proteins in ileal proteins in ileal carcinoidscarcinoids
RESULTSRESULTSIncreased expressions of c-MET and MTA-1 proteins in 78% and 79% of cases, respectively
Increased expression of VEGF in 11% of cases
No expression variations between primary and metastatic tumors
0
20
40
60
80
100
c-MET MTA-1 VEGF
NORMAL: score 0-2OVEREXPRESSED: score 3
CONCLUSIONSCONCLUSIONS
The proteins c-Met and MTA-1 likely have a specific role in the malignant progression of ileal carcinoids
Overexpression of VEGF could not be confirmed
in our study
The increased levels of the c-MET and MTA-1 proteins
may depend on the Her-2/neu overexpression already
documented in ileal carcinoids