Editorial
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Dec 21, 2009; 15(47): 5898-5906
Published online Dec 21, 2009. doi: 10.3748/wjg.15.5898
Invasive front of colorectal cancer: Dynamic interface of pro-/anti-tumor factors
Inti Zlobec, Alessandro Lugli
Inti Zlobec, Alessandro Lugli, Institute for Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland
Author contributions: Zlobec I and Lugli A were equally responsible for preparing, drafting and editing this manuscript.
Correspondence to: Dr. Inti Zlobec, PhD, Institute for Pathology, University Hospital Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland. izlobec@uhbs.ch
Telephone: +41-61-2652895 Fax: +41-61-2652966
Received: October 13, 2009
Revised: November 10, 2009
Accepted: November 17, 2009
Published online: December 21, 2009
Abstract

Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carcinoma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of “tumor budding”, a feature which can be highly specific for tumors showing an infiltrating tumor growth pattern. Importantly, tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact, several tumor-associated antigens such as CD3, CD4, CD8, CD20, Granzyme B, FOXP3 and other immunological or inflammatory cell types have been identified as potentially prognostic in patients with this disease. Evidence seems to suggest that the balance between pro-tumor (including budding and infiltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand, the infiltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other, the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features, such as the BRE and Gleason scores, the ratio of pro- and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.

Keywords: Colorectal cancer, Prognosis, Tumor invasive front, Tumor budding, Tumor growth pattern, Tumor infiltrating lymphocytes, Tumor immunity, Microsatellite instability