Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer PatientsReport as inadecuate




Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients - Download this document for free, or read online. Document in PDF available to download.

Cellular Oncology - Volume 31 2009, Issue 3, Pages 169-178



Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

Department of Pathology, Rijnland Hospital, Leiderdorp, The Netherlands



Copyright © 2009 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: For stage I–II colon cancer a significant number 5–25% of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment.

Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition EMT was analyzed: β-catenin, TGF-β-R2 and SMAD4.

Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4.

Results: Of 135 analyzed patients 34 25.2% showed a high proportion of stroma stroma-high and 101 74.8% a low proportion stroma-low. Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82. A high-risk group was identified with stroma-high and SMAD4 loss OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56; 12 of 14 85.7% patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related HZ 5.42, CI 2.13–13.82, p < 0.001.

Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.





Author: Wilma E. Mesker, Gerrit-Jan Liefers, Jan M. C. Junggeburt, Gabi W. van Pelt, Paola Alberici, Peter J. K. Kuppen, Noel F. Miranda,

Source: https://www.hindawi.com/



DOWNLOAD PDF




Related documents