Standop Jens, Andrianifahanana Mahefatiana, Moniaux Nicolas, Schneider Matthias, Ulrich Alexis, Brand Randall E, Wisecarver James L, Bridge Julia A, Büchler Markus W, Adrian Thomas E, Batra Surinder K, Pour Parviz M
UNMC Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA.
Pancreatology. 2005;5(1):44-58. doi: 10.1159/000084490. Epub 2005 Mar 15.
BACKGROUND/AIMS: The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed.
Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed.
Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland.
ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.
背景/目的：已有报道称，胰腺癌中ErbB2的过表达发生率在1%至80%之间，各不相同。然而，我们的常规检查发现，三种抗ErbB2生长因子受体抗体在胰岛和胰腺内神经节中始终呈现强免疫反应性。为了验证我们的发现，并了解报道中胰腺癌中ErbB2过表达频率存在差异的原因，我们进行了以下研究。
使用来自三家制造商的抗体，对12例正常胰腺、7例外科慢性胰腺炎病例、21例原发性胰腺腺癌、9例转移性胰腺腺癌和4例胰岛细胞瘤的组织样本进行免疫组化检查。研究纳入了培养的人胰岛细胞和胰腺癌细胞系，以及来自胃肠道、中枢神经系统和肾上腺的样本。为作比较，使用了乳腺癌组织和乳腺癌细胞，以及来自叙利亚金黄地鼠的选定组织。为验证结果，进行了蛋白质免疫印迹和Northern斑点印迹分析。
胰腺癌的癌细胞在体外和体内，ErbB2免疫染色表现出显著的异质性，从染色非常浅到染色很强不等。另一方面，在人类和地鼠中，均发现朗格汉斯胰岛、胰腺内和胰腺外神经节、以及中枢神经系统、脊髓和肾上腺中始终呈现强免疫染色。
ErbB2似乎在神经内分泌组织中发挥重要作用，可能参与这些细胞的发育和功能调节。这些因子与胰岛细胞激素的共同表达很可能导致胰腺癌中多种促生长途径的激活及其侵袭性行为。
