Publication
Still proliferating CD44/Ki67 tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival
Journal Paper/Review - Mar 29, 2021
Klose Johannes, Schmitt Annelene, Pernthaler Julia, Warschkow Rene, Büchler Markus W, Schneider Martin, Lasitschka Felix, Tarantino Ignazio
Units
Keywords
Aged
Antineoplastic Agents/therapeutic use
*Apoptosis
*Cell Proliferation
Female
Fluorouracil/therapeutic use
Humans
Hyaluronan Receptors/*metabolism
In Situ Nick-End Labeling
Ki-67 Antigen/*metabolism
Male
Middle Aged
*Neoadjuvant Therapy
*Proctectomy
Prognosis
Proportional Hazards Models
Radiotherapy
Rectal Neoplasms/metabolism/pathology/*therapy
Survival Rate
Treatment Outcome
*Distant recurrence
*Mediation analysis
*Neoadjuvant radiochemotherapy
*Rectal cancer
PubMed
Doi
Contact
Citation
Type
Journal
Publication Date
Issn Print
Issn Electronic
Pages
Brief description/objective
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.