Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 21, 2008; 14(7): 1060-1066
Published online Feb 21, 2008. doi: 10.3748/wjg.14.1060
Predictive value of Ki67 and p53 in locally advanced rectal cancer: Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy
Christiane Jakob, Torsten Liersch, Wolfdietrich Meyer, Heinz Becker, Gustavo B Baretton, Daniela E Aust
Christiane Jakob, Wolfdietrich Meyer, Gustavo B Baretton, Daniela E Aust, Institute for Pathology, University of Technology, Fetscherstr. 74, D-01307 Dresden, Germany
Torsten Liersch, Heinz Becker, Department of General, Visceral and Transplantation Surgery, University Medical Center of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany
Author contributions: Jakob C, Liersch T, and Aust DE designed the study; Liersch T helped with the acquisition of data; Jakob C and Meyer W did the statistical analyses of the data; Becker H helped supported the acquisition of material; Baretton GB revised the manuscript and provided technology and material support; Jakob C and Aust DE wrote and revised the manuscript.
Correspondence to: Dr. Christiane Jakob, Institute for Pathology, University of Technology, Fetscherstr. 74, D-01307 Dresden, Germany. christiane.jakob@uniklinikum-dresden.de
Telephone: +49-351-4585282
Fax: +49-351-4584328
Received: October 11, 2007
Revised: December 19, 2007
Published online: February 21, 2008
Abstract

AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.

METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage II/III) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.

RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.

CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.

Keywords: p53, Ki67, Neoadjuvant treatment, Rectal cancer, Thymidylate synthase