Differential clinical benefits of 5-fluorouracil-based adjuvant chemotherapy for patients with stage III colorectal cancer according to CD133 expression status.
OBJECTIVE
CD133 has been recently identified as a marker of putative cancer stem cells in colorectal tumors. The ability of cancer stem cells to resist chemotherapy was clinically highlighted; however, whether CD133 expression can predict chemoresistance remains controversial. The objective of the study was to determine the relationship between clinical benefits of adjuvant chemotherapy and CD133 expression status in colorectal cancer.


METHODS
We enrolled 234 patients with Stage III colorectal cancer who underwent curative resection. Among them, 149 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 85 did not (surgery-alone group). We immunohistochemically stained the specimens for CD133 on specimens evaluated the benefits of adjuvant chemotherapy according to CD133 expression using the Kaplan-Meier method and log-rank test.


RESULTS
A comparison of disease-free survival between both the groups revealed a significant 3-year disease-free survival benefit of adjuvant chemotherapy in CD133-negative (92.2% versus 74.5%; P = 0.004), but not in CD133-positive patients (46.8% versus 52.9%; P = 0.67). Multivariate analysis corroborated the benefits of adjuvant chemotherapy in CD133-negative (P = 0.003, hazard ratio = 0.26), but not in CD133-positive patients.


CONCLUSIONS
CD133-positive patients showed resistance to 5-FU-based chemotherapy, while CD133-negative patients experienced significant survival benefits from adjuvant chemotherapy not shared by CD133-positive patients.
*Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan. drs1793@ndmc.ac.jp.
Atsushi
A
Shikina
Eiji
E
Shinto
Yojiro
Y
Hashiguchi
Hideki
H
Ueno
Yoshihisa
Y
Naito
Koichi
K
Okamoto
Toru
T
Kubo
Satomi
S
Fukazawa
Junji
J
Yamamoto
Kazuo
K
Hase
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D005472:Fluorouracil
GI-Colorectum-Basic; GI-Colorectum-Med.; chemo-GI tract