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Still proliferating CD44/Ki67 tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival

Johannes Klose, Annelene Schmitt, Julia Pernthaler, Rene Warschkow, Markus W Büchler, Martin Schneider, Felix Lasitschka & Ignazio Tarantino

abstract

INTRODUCTION
Distant recurrence, especially liver metastases, occurs in one-third of rectal cancer patients initially treated with curative therapy and is still an unsolved problem. The identification of patients at risk is crucial for enabling individualized treatment.

MATERIAL AND METHODS
All patients undergoing curative resection for histologically confirmed rectal cancer after neoadjuvant radiochemotherapy between January 2001 and December 2015 were included. Sections were stained for Ki67, CD44, apoptosis and CD133. Patients were categorized based on whether they were found to have (CD44/Ki67) or not have (CD44/Ki67) still proliferating tumor cells.

RESULTS
218 patients who underwent R0 resection for stage I-III rectal cancer were selected. In 37 (17%) of these patients, CD44/Ki67 tumor cells were found. In multivariable Cox regression analysis, patients with CD44/Ki67 cells had significantly impaired overall (hazard ratio (HR): 3.84, 95% CI: 1.77-8.31, p = 0.001) and relative survival (HR 3.44, 95% CI: 1.46-8.09). The previous results were confirmed after propensity-score matching. In mediation-analysis, the presence of CD44/Ki67 cells was associated with a substantial direct effect on overall (HR 1.92, 95% CI: 1.09-9.28) and relative survival (HR 1.63, 95% CI: 1.31-6.38).

CONCLUSIONS
The presence of still proliferating CD44/Ki67 tumor cells after neoadjuvant radiochemotherapy was associated with impaired oncological long-term outcomes. Characterization of these cells should be performed.
   
citation Klose J, Schmitt A, Pernthaler J, Warschkow R, Büchler M W, Schneider M, Lasitschka F, Tarantino I. Still proliferating CD44/Ki67 tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival. Eur J Surg Oncol 2021;.
   
type journal paper/review (English)
date of publishing 29-03-2021
journal title Eur J Surg Oncol
ISSN electronic 1532-2157
PubMed 33814238
DOI 10.1016/j.ejso.2021.03.250