ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients.
OBJECTIVE
To analyze the expression of 8 putative cancer stem cell (CSC) markers within colorectal cancer tumor buds and to determine their prognostic impact in patients with this disease.


METHODS
Immunohistochemistry was performed on 101 colorectal cancer resections for CK22 (to identify tumor buds) as well as CD133, CD166, CD24, CD44s, CD90, EpCAM, ALDH1, and ABCG5, and their expression within tumor buds was evaluated.


RESULTS
CD90, CD44s, and CD133 expression in tumor buds was found in less than 5% of all cases. ALDH1, CD24, CD166 were expressed in 16.5%, 16.2%, and 34% cases, respectively, while ABCG5 and EpCAM expression was more frequent and found in 35% and 69% of cases, respectively. Of the 8 markers studied, EpCAM and ABCG5 positivity in tumor buds were significantly associated with poor prognosis (P = 0.023, P = 0.038, respectively) in multivariable analysis with pT and pN classification [P = 0.048; hazard ratio (HR): 2.64; 95% CI: 1.0-6.9, for EpCAM and P = 0.029; HR: 2.22; 95% CI: 1.0-4.5, for ABCG5]. Poor survival time was particularly striking for lymph node-negative patients with ABCG5-positive buds (P < 0.001).


CONCLUSIONS
Expression of putative stem cell markers EpCAM and ABCG5 within the tumor buds of colorectal cancer are frequently noted and are associated with poor prognosis.
Institute for Pathology, University Hospital of Basel, Schoenbeinstrasse 40, Basel CH-4031, Switzerland.
Lsabel
L
Hostettler
Inti
I
Zlobec
Luigi
L
Terracciano
Alessandro
A
Lugli
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies
C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D008074:Lipoproteins