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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma
Raluca Niculina Ciurea, Ion Rogoveanu, Daniel Pirici, Georgică-Costinel Târtea, Costin Teodor Streba, Cristina Florescu, Bogdan Cătălin, Ileana Puiu, Elena-Anca Târtea, Cristin Constantin Vere
Raluca Niculina Ciurea, Department of Pathology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Ion Rogoveanu, Costin Teodor Streba, Cristin Constantin Vere, Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Daniel Pirici, Department of Research Methodology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Georgică-Costinel Târtea, Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Cristina Florescu, Department of Cardiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Bogdan Cătălin, Elena-Anca Târtea, Department of Physiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Ileana Puiu, Department of Pediatrics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Author contributions: Ciurea RN, Rogoveanu I and Pirici D contributed equally to this work; Ciurea RN, Rogoveanu I and Pirici D designed, drafted and performed the research; Streba CT, Florescu C, Cătălin B, Puiu I and Târtea EA participated in writing, editing and reviewing of this manuscript; Târtea GC and Vere CC revised the paper and approved the final version.
Supported by the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, project No. PN-II-RU-TE-2014-4-0582, contract No. 160/01.10.2015.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the University of Medicine and Pharmacy of Craiova, Petru Rareș Street 2, 200349 Craiova, Romania (registration no. 53/19.05.2016).
Informed consent statement: All biological samples from the patients were taken after informed consent.
Conflict-of-interest statement: All the authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Georgică-Costinel Târtea, MD, PhD, Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Petru Rareș Street 2, 200349 Craiova, Romania. georgetartea@gmail.com
Telephone: +40-740-303735
Received: November 10, 2016
Peer-review started: November 11, 2016
First decision: December 19, 2016
Revised: December 26, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: February 21, 2017
AIM
To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.
METHODS
In this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.
RESULTS
B2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.
CONCLUSION
B2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.
Core tip: In the present study, we provide the first description of beta-2 adrenergic (B2A) receptors found on the nuclear membrane of colon adenocarcinoma cells. B2A receptors have a high level of expression in the neoplastic cells from colorectal adenocarcinoma, and a significant association was found between the expression of B2A receptors and tumor grading. Regarding the enteric nervous system and its associations with colorectal cancer, we observed a decrease of the relative area, both for Auerbach and Meissner plexuses, with the increase of the tumor grading, and an increase of the relative area of other nervous elements with the tumor grading.
