Lower Sympathetic Nervous System Density and β-adrenoreceptor Expression Are Involved in Gastric Cancer Progression

Abstract

Background/Aim: Identifying the role of the sympathetic nervous system (SNS) in tumor progression is among the most important challenges in cancer research. This study aimed to investigate the role of the SNS and beta-adrenoreceptor in gastric cancer progression. Materials and Methods: The density of SNS was quantified by immunohistochemical staining for tyrosine hydroxylase in 115 surgically-resected gastric cancer specimens. Immunostaining for beta 1- and beta 2-adrenoreceptor was also performed to examine the beta-adrenoreceptor expression status in gastric cancer. Then the association of protein expression status with histological grade, pathological tumor stage (pT), and pathological node stage of gastric cancer was investigated. Results: The SNS density of pT4 tumors was significantly lower than that of pT1-3 tumors. The SNS density was positively correlated with beta 1-adrenoreceptor expression status. In addition, lower beta 1-adrenoreceptor expression was significantly associated with increased lymph node metastasis. Reduced beta 2-adrenoreceptor staining proportion was significantly associated with worse histological grade. Furthermore, the proportion of beta 2-adrenoreceptor staining was significantly lower in tumors with diffuse-type histology, than those with intestinal-type histology. Conclusion: A lower SNS density and beta-adrenoreceptor expression was associated with an aggressive oncogenic behavior including worse histological grade, advanced pT, and increased lymph node metastasis. SNS and beta-adrenergic pathway are involved in the negative regulation of gastric cancer progression.