Enrichment of CD133‐expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival

Medientyp: E-Artikel
Titel: Enrichment of CD133‐expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival
Beteiligte: Sprenger, Thilo; Conradi, Lena‐Christin; Beissbarth, Tim; Ermert, Heiko; Homayounfar, Kia; Middel, Peter; Rüschoff, Josef; Wolff, Hendrik A.; Schüler, Philipp; Ghadimi, B. Michael; Rödel, Claus; Becker, Heinz; Rödel, Franz; Liersch, Torsten
Erschienen: Wiley, 2013
Erschienen in: Cancer
Sprache: Englisch
DOI: 10.1002/cncr.27703
ISSN: 0008-543X; 1097-0142
Schlagwörter: Cancer Research ; Oncology
Entstehung:
Anmerkungen:
Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND:</jats:title><jats:p>The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as <jats:italic>Prominin</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>METHODS:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>RESULTS:</jats:title><jats:p>Compared with pre‐RCT biopsies, significantly higher CD133 expression was observed in tumor specimens (<jats:italic>P</jats:italic> = .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 (<jats:italic>P</jats:italic> = .02) and lower histopathologic tumor regression (<jats:italic>P</jats:italic> < .01). Moreover, these patients had significantly reduced disease‐free survival and cancer‐specific overall survival in univariate analysis (<jats:italic>P</jats:italic> < .001 and <jats:italic>P</jats:italic> = .004, respectively) and multivariate analysis (<jats:italic>P</jats:italic> = .003 and <jats:italic>P</jats:italic> = .024, respectively).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS:</jats:title><jats:p>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. Cancer 2013. © 2012 American Cancer Society.</jats:p></jats:sec>
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