Kantonsspital St.Gallen

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


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.

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.

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).

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.
keywords Adenocarcinoma/metabolism/pathology/*therapy
Antineoplastic Agents/therapeutic use
*Cell Proliferation
Fluorouracil/therapeutic use
Hyaluronan Receptors/*metabolism
In Situ Nick-End Labeling
Ki-67 Antigen/*metabolism
Middle Aged
*Neoadjuvant Therapy
Proportional Hazards Models
Rectal Neoplasms/metabolism/pathology/*therapy
Survival Rate
Treatment Outcome
*Distant recurrence
*Mediation analysis
*Neoadjuvant radiochemotherapy
*Rectal cancer
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; 47:2078-2086.
type journal paper/review (English)
date of publishing 29-3-2021
journal title Eur J Surg Oncol (47/8)
ISSN print 0748-7983
ISSN electronic 1532-2157
pages 2078-2086
PubMed 33814238
DOI 10.1016/j.ejso.2021.03.250
contact Ulrich Beutner