Tumor budding at the invasive tumor front of colorectal cancer is recognized as an independent prognostic factor significantly related to both lymph node and distant metastasis. Several lines of evidence seem to suggest that tumor buds may, to some extent, represent malignant colorectal cancer stem cells because of their potential for migration and re-differentiation locally and at sites of metastasis. However, phenotypic characterization of cancer stem cells in general is still debated although at least 8 putative stem cell markers have been suggested including CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. Little is known about the potential of these proteins to act as prognostic biomarkers in patients with colorectal cancer and most of these proteins have never before been explored within tumor buds themselves.
A research article published on February 14, 2010 in the World Journal of Gastroenterology addressed this question. Considering the apparent stem cell-like properties of tumor buds and association of budding with adverse clinical outcomes, the research team led by Dr. Alessandro Lugli performed immunohistochemical staining of 8 putative cancer stem cell markers, namely CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. The expression within tumor buds was evaluated, their frequency of occurrence and their potential prognostic significance in patients with colorectal cancer were determined.
Their findings showed that expression of EpCAM and particularly of ABCG5 within the tumor buds of colorectal cancer are frequent events. Moreover, expression of EpCAM or ABCG5 within tumor buds themselves has the potential to stratify patients with colorectal cancer into prognostic subgroups. This was particularly pronounced for patients with node-negative disease.
The results of this study could have important implications for patients with lymph node-negative colorectal cancer. Stratification of this group of patients could help to identify those likely to have a particularly poor outcome who could perhaps be considered for adjuvant therapy.
The study is characterized technically by an excellent application of immunohistochemistry and provides interesting evidence to aid the understanding of the correlation between cancer stem cell markers at the invasive front of colorectal cancer and prognosis. The findings suggest that EpCAM and ABCG5 in tumor buds may be useful biomarkers of poor outcome in this subgroup of patients. However, further studies are necessary to address the important issue of whether EpCAM- or ABCG5-positive tumor buds indeed represent migrating colorectal cancer stem cells.
Reference: Hostettler I, Zlobec I, Terracciano L, Lugli A. ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients. World J Gastroenterol 2010; 16(6): 732-739
Correspondence to: Dr. Alessandro Lugli, MD, Institute for Pathology, University Hospital of Basel, Schoenbeinstrasse 40, Basel, CH-4031, Switzerland. email@example.com
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About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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