Original ContributionsImmunohistochemical expression of transforming growth factor α and epidermal growth factor receptor in pancreatic endocrine tumors*
Section snippets
Materials and methods
Thirty-five PETs (21 benign and 14 malignant) were retrieved from the surgical pathology files of the New England Medical Center for the study. All original hematoxylin and eosin (H & E)–stained slides on each of these cases were reviewed to confirm the diagnosis and to select representative paraffin blocks with tissues adequate enough to yield 30 to 35 serial sections. Metastatic lesions were included for study only if sufficient tissue material was available on both the primary tumor and the
Results
The 21 benign and 14 malignant PETs included in the study were obtained from 10 male and 25 female patients ranging in age from 11 to 76 years. Twenty tumors were associated with a functional syndrome and could be categorized as insulinoma (n = 10), gastrinoma (n = 7), VIPoma (n = 2), and GHRF-producing tumors (n = 1) based on the dominant secretory product (see below). The other 15 tumors were clinically nonfunctional. The 14 malignant tumors (with demonstrable metastases) varied in size from
Discussion
Cellular growth and/or differentiation is normally initiated when extracellular growth factors bind with their specific transmembrane receptors and send a physical signal through the cell membrane. Inside the cell, this signal is propagated by activation of an enzyme, usually a tyrosine-specific kinase that is either intrinsic to or closely associated with the cytoplasmic face of the receptor.25, 26 A variety of different intracellular proteins then carry the signal to the nucleus, where
References (38)
- et al.
Growth factors in development, transformation and tumorigenesis
Cell
(1991) - et al.
Autocrine growth factors and tumorigenic transformation
Immunol Today
(1990) - et al.
Signal transduction by receptors with tyrosine kinase activity
Cell
(1990) - et al.
Human term placenta contains transforming growth factors
Biochem Biophys Res Commun
(1982) - et al.
Growth factor signaling by receptor tyrosine kinases
Neuron
(1992) Molecular themes in oncogenes
Cell
(1991)- et al.
Transforming growth factor-alpha in normal and neoplastic human endocrine tissues
Hum Pathol
(1992) - et al.
Heterodimerization and functional interaction between EGFR receptor family members: A new signaling paradigm with implications for breast cancer research
Breast Cancer Res Treat
(1995) - et al.
Localization of transforming growth factor-α and it's receptor in gastric mucosal cells. Implications for a regulatory role in acid secretion and mucosal renewal
J Clin Invest
(1989) - et al.
Production and auto-induction of transforming growth factor-α in human keratinocytes
Nature
(1987)
Ovarian transforming growth factor-α gene expression: Immunohistochemical localization to theca-interstitial cells
Endocrinology
Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer
J Pathol
Synthesis of messenger RNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumors
Cancer Res
Expression of transforming growth factor alpha in primary human colon and lung carcinomas
Br J Cancer
Growth factors and carcinoid tumors
Acta Oncol
Mucosal expression and luminal release of epidermal and transforming growth factors in patients with duodenal ulcer before and after eradication of H. pylori
Gut
The EGFR is present on the basolateral but not the apical surface of enterocytes in the human GI tract
Gut
Gastric epithelial cell kinetics in the progression of normal gastric mucosa to gastric carcinoma
Gut
Increased susceptibility to N-nitrosomethylurea gastric carcinogenesis in transforming growth factor alpha transgenic mice with gastric hyperplasia
Jpn J Cancer Res
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Highly sensitive detection of epidermal growth factor receptor expression levels using a capacitance sensor
2015, Sensors and Actuators, B: ChemicalCitation Excerpt :Among biomarkers, an epidermal growth factor receptor (EGFR), which is a transmembrane glycoprotein on cell membrane, has considerable attentions as one of the effective cancer biomarkers in recent researches [6–8]. The high EGFR expression level have quite been discovered in tumor progression [9–13], cancer cell proliferation and metastatic phenotype [14–16]. In other words, observing over-expressed EGFR can indicate that the cells are likely to be identified as cancer cells [17,18].
Pancreatic endocrine tumours: Mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries
2012, Annals of OncologyCitation Excerpt :This is particularly important when targeting receptor tyrosine kinases (RTKs) with the use of monoclonal antibodies or inhibitors of their tyrosine kinase activity [22–26]. About the presence and role of protein kinases, particularly of RTKs, in PETs, inconsistent results have been reported [27–35]. In the present study, we explored the kinome searching a panel of 36 primary PETs and 3 PET cell lines for mutations in 35 kinase genes including: 25 genes frequently mutated in human cancers other than pancreatic [18–21], 6 genes related to the Akt-mTOR pathway that has been shown to be activated in PET [17], and 4 genes encoding for RTKs targeted by available anticancer drugs.
Molecular target therapy for gastroenteropancreatic endocrine tumours: Biological rationale and clinical perspectives
2009, Critical Reviews in Oncology/HematologyCitation Excerpt :The majority (80%) of patients in this study experienced SD as the best response to treatment but, as already stressed, this observation might reflect the intrinsic indolent nature of these tumours, as part of the study group had stable disease before entry as well. The surface of GEP ET cells presents several growth factor receptors, including receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR), the stem cell factor (SCF) receptor c-KIT and the platelet derived growth factor receptor [45–48]. At present, a number of different drugs specifically designed to block the activation of these targets and their downstream pathways are available.
Epidermal growth factor receptor distribution in pericoronal follicles: relationship with the origin of odontogenic cysts and tumors
2007, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodontologyCitation Excerpt :We observed 7 nests with membrane-only staining. Membrane-only staining is found in areas and tissues with greater proliferative potential23,34,35 in the presence of factors such as the EGF and the TGF-α. The low frequency of membrane-only staining observed in odontogenic epithelial nests in the present study could explain the rarity of odontogenic tumors arising from nests.
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2019, Endocrine-Related CancerGastroenteropancreatic neuroendocrine tumor microenvironment and related therapy
2019, Zhonghua Wai Ke Za Zhi / Chinese Journal of Surgery
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Address correspondence and reprint requests to Yogeshwar Dayal, MD, Department of Pathology, New England Medical Center, 750 Washington St, Boston, MA 02111.