Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Dec 10, 2016; 7(6): 433-440
Published online Dec 10, 2016. doi: 10.5306/wjco.v7.i6.433
Circulating cytokeratin-positive cells and tumor budding in colorectal cancer
Bruno Märkl, Narjes Wilhelms, Matthias Anthuber, Gerhard Schenkirsch, Günter Schlimok, Daniel Oruzio
Bruno Märkl, Narjes Wilhelms, Institute of Pathology, Klinikum Augsburg, 86156 Augsburg, Germany
Matthias Anthuber, Department of Visceral Surgery, Klinikum Augsburg, 86156 Augsburg, Germany
Gerhard Schenkirsch, Clinical and Population-Based Cancer Registry Augsburg, 86156 Augsburg, Germany
Günter Schlimok, Hematology and Oncology, Diakonissenkrankenhaus Augsburg, 86156 Augsburg, Germany
Daniel Oruzio, Onkologische Praxis MVZ, 86508 Rehling, Germany
Author contributions: Märkl B designed the study, collected the blood samples, performed the statistical analyses and drafted the manuscript; Wilhelms N collected the data, completed the follow-up data, was responsible for the graphics and revised the manuscript; Anthuber M was responsible for the surgical component and informed consent and provided analytical oversight; Schenkirsch G provided follow-up data and revised the manuscript; Schlimok G was involved in designing the study and provided analytical oversight; Oruzio D was responsible for the immunocytochemical analysis and revised the manuscript; all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the Ethikkomission der Landesärztekammer Bayern.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare that no conflicting interests (including but not limited to commercial, personal, political, intellectual or religious interests) exist.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at bruno.maerkl@klinikum-augsburg.de. Participants consent was not obtained but the presented data are anonymized and risk of identification is low.
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: Dr. med. Bruno Märkl, MD, PhD, Institute of Pathology, Klinikum Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany. bruno.maerkl@klinikum-augsburg.de
Telephone: +49-821-4003199 Fax: +49-821-400173199
Received: August 3, 2016
Peer-review started: August 5, 2016
First decision: September 2, 2016
Revised: September 10, 2016
Accepted: October 17, 2016
Article in press: October 19, 2016
Published online: December 10, 2016
Processing time: 118 Days and 11.4 Hours
Abstract
AIM

To investigate whether circulating cytokeratin-positive (CK+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding.

METHODS

Fifty-six colorectal specimens were collected between 9/2007 and 7/2008. Blood from the mesenteric vein was drawn immediately after receiving the fresh and unfixed specimens in the pathology department. After separation of the mononuclear cells by Ficoll-Hypaque density-gradient centrifugation, cytological smears were immunocytochemically stained for CK18. Tumor budding was evaluated on slides stained for pan-cytokeratin. The identification of ≥ 30 buds/1.3 mm2 was defined as high grade budding.

RESULTS

CK+ cells and clusters were identified in 29 (48%) and 14 (25%) of the samples, respectively. Two cells were identified in one of three non-malignant cases. Clusters were found exclusively in malignant cases. The occurrence of CK+ cells or clusters was not associated with any of the evaluated clinicopathological factors, including surgical technique and tumor budding. Moreover, the occurrence of CK+ cells or clusters had no influence on the cancer-specific survival [75 mo (CI: 61; 88) vs 83 mo (CI: 72; 95) and 80 mo (CI: 63; 98) vs 79 mo (CI: 69; 89), respectively].

CONCLUSION

CK+ cells and showed neither prognostic significance nor an association with tumor budding. It is very likely that CK18-staining is not specific enough to identify the relevant cells.

Keywords: Colorectal cancer; Circulating cells; Tumor budding; Peripheral blood; Survival

Core tip: Blood from the mesenteric vein of 56 colorectal specimens was drawn and evaluated for CK18 positive epithelial cells (CK+). CK+ cells and clusters were identified in a high proportion of cases. However, these cells and clusters were not associated with any of the evaluated clinicopathological factors, including surgical technique and tumor budding. Moreover, the occurrence of CK+ cells or clusters had no influence on the cancer specific survival. Immunocytochemical staining for CK18 does not seem to be a specific marker of mesenteric blood cells for prognostic identification of relevant circulating tumor cells.