Enrichment of CD133-expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival.
BACKGROUND
The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as Prominin or PROM1) has been described as a potential stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study, CD133 expression was evaluated in pre-RCT tumor biopsies and the corresponding post-RCT surgical specimens from patients with locally advanced rectal adenocarcinoma, and expression levels were correlated with histopathologic features and clinical follow-up.


METHODS
One hundred twenty-six patients with International Union Against Cancer (UICC) stage II/III rectal cancer who received preoperative 5-fluorouracil (5-FU)-based RCT within the German Rectal Cancer Trials were investigated. Pre-RCT and post-RCT CD133 expression levels were determined using immunohistochemistry and were correlated with histopathologic parameters, tumor regression grade, cancer recurrence, and patient survival.


RESULTS
Compared with pre-RCT biopsies, significantly higher CD133 expression was observed in tumor specimens (P = .01). However, no correlations were observed for either biopsies or tumor specimens between CD133 expression levels, histopathologic characteristics, or survival. In matched analyses of corresponding biopsy/tumor pairs, patients who had an increased fraction of CD133-expressing (CD133+) cells after preoperative RCT had significantly higher residual tumor stages (P = .02) and lower histopathologic tumor regression (P < .01). Moreover, these patients had significantly reduced disease-free survival and cancer-specific overall survival in univariate analysis (P < .001 and P = .004, respectively) and multivariate analysis (P = .003 and P = .024, respectively).


CONCLUSIONS
The enrichment of CD133+ cancer cells during preoperative RCT was correlated with minor local tumor response, increased distant cancer recurrence, and decreased survival. The current results indicate that the up-regulation of intratumoral CD133 expression, in contrast to absolute pre-RCT and post-RCT CD133 levels, plays an important role in tumor progression and metastasis in patients with rectal cancer who are receiving neoadjuvant RCT.
Department of General and Visceral Surgery, University Medical Center, Goettingen, Germany. tsprenger@chirurgie-goettingen.de
Thilo
T
Sprenger
Lena-Christin
LC
Conradi
Tim
T
Beissbarth
Heiko
H
Ermert
Kia
K
Homayounfar
Peter
P
Middel
Josef
J
Rüschoff
Hendrik A
HA
Wolff
Philipp
P
Schüler
B Michael
BM
Ghadimi
Claus
C
Rödel
Heinz
H
Becker
Franz
F
Rödel
Torsten
T
Liersch
D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides