ArticleVirchows Archiv : an international journal of pathology2011
Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors.
Article in Virchows Archiv : an international journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?Reviews in endocrine & metabolic disorders · 2021Review
- Management of Typical and Atypical Pulmonary Carcinoids Based on Different Established Guidelines.Cancers · 2018Review
- Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology.Cellular and molecular gastroenterology and hepatology · 2015Review
- PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.Theranostics · 2014Review
- Histopathology of gastrointestinal neuroendocrine neoplasms.Frontiers in oncology · 2013Article
- Development of a novel monoclonal antibody to B7-H4: characterization and biological activity.European journal of medical research · 2011Article
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Authors and funding
9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
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.
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