Immunohistochemical expression of transforming growth factor α and epidermal growth factor receptor in pancreatic endocrine tumors

Srivastava, Amitabh; Alexander, J. H.; Lomakin, Inna; Dayal, Yogeshwar

doi:10.1053/hupa.2001.28959

Cited by 39 publications

(25 citation statements)

References 33 publications

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“…Adjacent sections were stained for gastrin (a) and insulin (b) and imaged at ×40 magnification. Inserts show parts of the same sections at ×200 magnification cell replication adjacent to gastrinomas is the increased beta cell proliferation in the absence of gastrin staining and despite the low gastrin content in tumour lysates observed in the present as well as in previous studies [19,29]. Moreover, the expansion of beta cell mass previously shown in rodent studies was much more pronounced during the combined administration of EGF and gastrin than with gastrin alone [11,12].…”

Section: Discussionsupporting

confidence: 60%

Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

Meier¹,

Butler²,

Galasso³

et al. 2006

Diabetologia

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Aims/hypothesis Type 1 and type 2 diabetes are characterised by a beta cell deficit. Islet hyperplasia has been described in patients with Zollinger-Ellison syndrome secondary to gastrin-producing tumours (gastrinomas), and gastrin therapy has increased beta cell mass in rodents and human islets in vitro. In the present studies we addressed the following questions: (1) In pancreas specimens from gastrinoma cases, is the fractional beta cell area increased? (2) If so, is this restricted to tumour-adjacent islets or also present in tumour-distant islets? (3) Is new beta cell formation (beta cell replication and islet neogenesis) increased and beta cell apoptosis decreased in pancreas specimens from gastrinoma cases? Methods Pancreas was obtained at surgery from four patients with Zollinger-Ellison syndrome caused by pancreatic gastrinomas and 15 control subjects at autopsy. Results Islet fractional beta cell area (p<0.001), islet size (p<0.001) and beta cell replication (Ki67 staining) (p<0.05) were increased in islets adjacent to the tumours, but not in tumour-distant pancreas, compared with control subjects. We did not observe any differences in beta cell apoptosis or in the number of insulin-positive cells in ducts either adjacent to or distant from the tumour. Conclusions/interpretationOne or more factors released by human gastrinomas increase beta cell replication in islets immediately adjacent to the tumour, but not in tumourdistant islets. While these findings demonstrate that adult human beta cells can be driven into the cell cycle, they caution against the therapeutic usefulness of gastrin, since islets located >1 cm away from the gastrinomas did not exhibit changes in beta cell turnover, despite markedly elevated systemic gastrin levels sufficient to cause severe gastrointestinal symptoms.

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Section: Discussionsupporting

confidence: 60%

Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

Meier¹,

Butler²,

Galasso³

et al. 2006

Diabetologia

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“…Although earlier studies examined EGFR expression in carcinoids and pancreatic endocrine tumors, [4][5][6][7][8] this study is the first to examine activated or P-EGFR in these tumors. Western blot analysis supported the immunohistochemical observations of EGFR and P-EGFR expression by the detection of a 170 kDa protein band in primary and metastatic carcinoid tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have shown that EGFR is expressed in carcinoids and pancreatic endocrine tumors. [4][5][6][7][8] However, the activated or phosphorylated form of EGFR (P-EGFR) has been examined in only a few neuroendocrine tumors, 9 and it has not been studied in primary gastrointestinal carcinoid or pancreatic endocrine tumors.…”

mentioning

confidence: 99%

Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas

et al. 2005

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The epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of many tumors. To analyze the expression of EGFR and activated EGFR in well-differentiated neuroendocrine carcinomas including primary and metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors (PET), we examined 58 gastrointestinal carcinoid tumors and 48 PET using immunohistochemistry, Western blotting, and RT-PCR. EGFR and activated EGFR (P-EGFR) were expressed by both gastrointestinal carcinoids and PET in primary and metastatic tumors, although a higher percentage of gastrointestinal carcinoid tumors expressed EGFR and activated EGFR. Western blotting detected a 170 kDa band for both EGFR and activated EGFR in three primary carcinoid tumors and two metastatic carcinoid tumors to the liver. RT-PCR analysis confirmed the expression of EGFR mRNA in both primary and metastatic carcinoid tumors. Patients with activated EGFR expression in their primary PET had a significantly worse prognosis compared to those who did not express activated-EGFR (P ¼ 0.043). These results indicate that gastrointestinal carcinoid tumors as well as PET express EGFR and activated EGFR, and that expression is more common in gastrointestinal carcinoid tumors compared to pancreatic endocrine tumors. These findings implicate the EGFR and P-EGFR signal transduction pathway in the pathogenesis of these neuroendocrine tumors and suggest that targeted therapy directed against the EGFR tyrosine kinase domain may be a useful therapeutic approach in patients with unresectable metastatic gastrointestinal carcinoid tumors and pancreatic endocrine tumors.

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“…It was found to be unrelated to the tumour size or to the occurrence of metastases but was more frequent in tumours infiltrating the muscularis propria than in those limited to the mucosa/submucosa, suggesting a role for local invasion (Krishnamurthy & Dayal 1997). In pancreatic endocrine tumours different patterns ranging from full expression of TGF-α and of the complete EGFR molecule to the expression of only one of the two antigens or to the absence of both were found (Srivastava et al 2001). These patterns showed no correlation with size, functional status or biological behaviour of the tumours, indicating no role for TGF-α in tumour progression.…”

Section: Transforming Growth Factor-α (Tgf-α)mentioning

confidence: 95%

Highlights of the biology of endocrine tumours of the gut and pancreas.

Rindi

Bordi²

2003

Endocrine-Related Cancer

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Originating from cells of the diffuse endocrine system the endocrine tumours of the gut and the pancreatic tract are rare entities characterized by a common phenotypic aspect and producing several bioactive substances including growth factors. Two major categories are identified: well-differentiated and poorly differentiated tumours. The clinical behaviour varies ranging from benign to low grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The two major categories of well-differentiated and poorly differentiated tumours display distinct phenotypes and genetic backgrounds possibly supporting distinct histogenesis. Genetic abnormalities associated with either induction or progression of tumours may vary depending on the site of origin.

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Immunohistochemical expression of transforming growth factor α and epidermal growth factor receptor in pancreatic endocrine tumors

Cited by 39 publications

References 33 publications

Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas

Highlights of the biology of endocrine tumours of the gut and pancreas.

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