Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2017; 9(11): 444-451
Published online Nov 15, 2017. doi: 10.4251/wjgo.v9.i11.444
Value of histomorphometric tumour thickness and smoothelin for conventional m-classification in early oesophageal adenocarcinoma
Katharina Endhardt, Bruno Märkl, Andreas Probst, Tina Schaller, Daniela Aust
Katharina Endhardt, Bruno Märkl, Tina Schaller, Institute of Pathology, Klinikum Augsburg, Augsburg 86156, Germany
Andreas Probst, Department of Gastroenterology, Klinikum Augsburg, Augsburg 86156, Germany
Daniela Aust, Institute of Pathology, Universitätsklinikum Dresden, Dresden 01307, Germany
Author contributions: Endhardt K, Märkl B, Probst A and Aust D contributed to study conception and design; Schaller T contributed to data acquisition, data analysis, and interpretation; Endhardt K, Märkl B and Aust D contributed to data acquisition, data analysis, and interpretation writing of article; all authors contributed to editing, reviewing and final approval of the article; Endhardt K and Märkl B contributed equally to this work.
Institutional review board statement: The study has been approved by the internal review board of the Klinikum Augsburg (Review-Number: BKF 2015-13).
Informed consent statement: Informed consent statement was not required because of the design of a retrospective observational study. The study was performed in accordance to the national laws (Bayerisches Krankenhausgesetz).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data set and search algorithms are available from the corresponding author at
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:
Correspondence to: Bruno Märkl, MD, Institute of Pathology, Klinikum Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany.
Telephone: +49-821-4003199 Fax: +49-821-400173199
Received: July 8, 2017
Peer-review started: July 19, 2017
First decision: August 7, 2017
Revised: August 17, 2017
Accepted: September 4, 2017
Article in press: September 5, 2017
Published online: November 15, 2017

To test the validity of tumour thickness measurement in distinguishing between the different infiltration depths, especially when the duplication of muscularis mucosae cannot be demarcated clearly.


We re-evaluated 100 completely embedded Barrett’s adenocarcinomas regarding m-classification, maximum tumour thickness, and muscularis mucosae duplication. For validation, smoothelin staining was performed on a subset of cases.


The m1-, m2- and m3-classified adenocarcinomas showed a significant lower tumour thickness compared to the m4- and sm1-classified lesions (P < 0.001). Smoothelin staining determined a clear muscularis mucosae duplication in 64% of the tested samples and enabled the differentiation of the two layers in diffuse and merged splits.


Tumour thickness in early oesophageal adenocarcinoma significantly correlates with the depth of infiltration and demonstrates its worth as an accurate pT classification in non-polypoid lesions. We created a new algorithm, which combines histomorphology with morphometric analyses. It is noteworthy that it facilitates the assessment of mucosal vs submucosal infiltration depth. The smoothelin staining strengthened our results of the tumour thickness evaluation and can be used in cases of doubt.

Keywords: Smoothelin, Endoscopic submucosal dissection, Muscularis mucosae, Barrett’s carcinoma

Core tip: The aim of this study was to determine whether histomorphometric measurement of tumor thickness and immunohistochemical staining for smoothelin facilitate the exact pT substaging in early oesophageal adenocarcinoma. Our data showed that there is clear cut-off of 1000 μm to distinguish advanced early lesions (M4/sm1) from such lesions that do not reach the deep muscularis mucosae or the submucosa. Moreover, smoothelin staining is of help to distinguish the superficial from the deep muscularis mucosa by different staining intensities. Therfore, both methods could be shown to be of help for the often challenging task to T-classify early oesophageal adenocarcinomas.