ABCG5 is a member of the ATP-binding cassette subfamily G and plays a role in the efflux transport of cholesterol[36,37]. Its expression has been correlated with clinical melanoma progression and it is hypothesized to contribute to the refractoriness of metastatic cancer to chemotherapy[38]. these Indeed, specific targeting of ABCG5 with monoclonal antibodies appears to significantly inhibit cell growth. To date, ABCG5 does not appear to have been investigated in colorectal cancer, and moreover in tumor buds. However, our findings of ABCG5 expression in a considerable number of colorectal cancer tumor buds as well as an adverse prognosis in particular in patients with lymph node-negative disease suggests that the role of ABCG5 in colorectal pathogenesis warrants further investigation.

Our results of adverse prognosis in EpCAM-positive and ABCG5-positive patients may be to some extent affected by the lack of information regarding cancer treatment. Despite this limitation, the unfavorable outcome associated with EpCAM and, particularly with ABCG5-positivity was maintained in patients with lymph node-negative colorectal cancers who, by today��s treatment guidelines, are not generally considered for adjuvant chemotherapy[39]. The findings of this study regarding the prognostic value and expression of EpCAM and ABCG5 within colorectal tumor buds should be considered preliminary and require validation on independent patient cohorts. To summarize, in contrast to CD133, CD166, CD24, CD44s, CD90, and ALDH1, the expression of putative stem cell markers EpCAM and ABCG5 within the tumor buds of colorectal tumors are frequent events indicating poor prognosis.

In particular, patients with lymph node-negative disease expressing EpCAM or ABCG5 have a particularly unfavorable prognosis suggesting that the immunohistochemically analyzed EpCAM and ABCG5 in tumor buds may be useful biomarkers of poor outcome in this subgroup of patients. Further studies are necessary to address the important issue of whether EpCAM- or ABCG5-positive tumor buds indeed represent migrating colorectal CSC. COMMENTS Background Tumor budding at the invasive tumor front of colorectal cancer is recognized as an important independent prognostic factor. 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. Research frontiers Phenotypic characterization of cancer stem cells is still debated although at least 8 putative stem cell markers have Brefeldin_A been suggested including CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5.