Elsevier

Pancreatology

Volume 15, Issue 6, November–December 2015, Pages 661-666
Pancreatology

Original article
Immunohistochemical examination of cholecystokinin and gastrin receptors (CCK-2/gastrin-R) expression in normal and exocrine cancerous human pancreatic tissues

https://doi.org/10.1016/j.pan.2015.09.019Get rights and content

Abstract

Objective

Evaluating 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.

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; ten (10) of them were normal pancreatic samples; and ten (10) cancerous pancreatic sections. The samples were studied using an immunohistochemical protocol for CCK-2/gastrin receptors.

Results

Our immunohistochemical analysis revealed that CCK-2/gastrin receptors were expressed in both normal and malignant pancreatic cells but with different immunoreactivity levels and different immunostaining intensity i.e., CCK-2/gastrin receptors were highly expressed within the cytoplasmic area of cancerous cells; 40% of the samples had an immunoreactivity (IR) of (+++) and 60% (++++); the immunostaining was as well very intense since we reported a dark brown staining of the malignant cells. However; in normal pancreatic tissues; CCK-2/gastrin receptors IR levels were very low; 80% of the samples had an IR of (+); and 20% had (++) and the immunostaining was less intense; we noted a light brown staining of few normal pancreatic cells.

Conclusion

The gastrointestinal peptides CCK could be very interesting targets for exocrine pancreatic cancer therapies; thus further surveys such as western blotting and RTPCR could indentify CCK-2/gastrin receptors as a helpful biomarker for exocrine pancreatic cancer diagnosis and treatment.

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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