Original articleImmunohistochemical examination of cholecystokinin and gastrin receptors (CCK-2/gastrin-R) expression in normal and exocrine cancerous human pancreatic tissues
Introduction
A role for cholecystokinin (CCK) and gastrin in the normal and diseased pancreas, particularly in pancreatic cancer, has been claimed for many years [1]. In the gastrointestinal tract, CCK and gastrin act as regulators of gastric acid secretion, gastric emptying and gall bladder motility [2].
The biological effects of CCK are mediated by two distinct G protein-coupled receptors, CCK1 (formerly CCK-A) and CCK2 (formerly CCK-B), which can be distinguished pharmacologically by their low affinity (CCK1) versus high affinity (CCK2) for gastrin [3], [4].
In humans, however, in contrast to rodents, there are numerous conflicting data on CCK2 expression in normal and diseased human pancreas [5], [6].
Several lines of evidence support the role of gastrin, the digestive peptide hormone and its G protein-coupled receptor (CCK2/gastrin-R) in pancreatic cancer development. In contrast, Ohlsson and co-workers reported that gastrin/cck2 had no growth promoting effect on human pancreatic cancer cell-lines derived from pancreatic cancer biopsy specimens obtained at surgery [1], [7].
In a recent survey; we suspected that cholecystectomy could be a risk factor for pancreatic cancer due to the increase serum levels of CCK and the suppression of the normal inhibitory effect of cholecystokinin ([26], [27], [28]).
The aim of our study was to evaluate tissue samples of normal and exocrine cancerous human pancreas on the expression of CCK2/gastrin receptor. We performed an immunohistochemical protocol that allows efficient detection of this receptor in formalin-fixed, paraffin-embedded human tissues.
Section snippets
Materials and methods
Twenty [20] paraffin blocks of pancreatic tissue sections were collected from the Departments of pathology, Central University Hospital of Sidi Bel Abbes City (Western Algeria) for the period 2004–2013; 10 of them were normal pancreatic tissues that were taken from patients with pancreatitis; and 10 cancerous pancreatic sections among them 9 pancreatic adenocarcinomas and 1 solid pseudopapaillary pancreatic tumour. These specimens were paraffin embedded in the same center. The cases were
Results
Ten patients with pancreatic cancer; and ten samples of normal pancreatic tissue were included in the current study. Median age of the patients with pancreatic cancer was 49 years (range, 28–70). There were 6 (60%) males and 4 (40%) females; male to female ratio was about 1.5 (Table 1). The most common site of the tumor was the head of the pancreas which was involved in 9 cases (90%), followed by the body and the tail of the pancreas involved in 1 case (10%).
As shown in Table 1 the most common
Discussion
Several inquiries were performed in order to study the distribution of cholecystokinin receptors throughout the gastrointestinal tract and diseased pancreas; nevertheless; very few were made to compare immunohistochemical expression of cholecystokinin-2 receptors in normal pancreatic human cells and malignant ones.
The data presented evaluate the expression of CCK-2/gastrin receptors by immunohistochemistry in samples from normal and exocrine cancerous human pancreatic tissue specimens. They
Conclusion
The gastrointestinal peptide CCK could be very interesting target for exocrine pancreatic cancer therapies; thus further surveys about immunohistochemical expression of cholecystokinin receptors as well as western blotting and RTPCR could indentify CCK-2/gastrin receptors as a helpful biomarker for exocrine pancreatic cancer diagnosis and treatment.
Acknowledgments
The authors would like to thank the members of pathology department of Sidi bel Abbes hospital for their invaluable support, guidance, and educational insight.
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