Cancer Chemother Pharmacol (2009) 64:391–398
DOI 10.1007/s00280-008-0886-4
123
ORIGINAL ARTICLE
Topoisomerase I and II protein expression in primary colorectal
cancer and recurrences following 5-Xuorouracil-based adjuvant
chemotherapy
Nicolas Tsavaris · Andreas Lazaris · Christos Kosmas · Panagiotis Gouveris ·
Nikolaos Kavantzas · Petros Kopterides · Thomas Papathomas · George Arapogiannis ·
Haralambos Zorzos · Vassiliki Kyriakou · Efstathios Patsouris
Received: 2 September 2008 / Accepted: 21 November 2008 / Published online: 16 December 2008
© The Author(s) 2008. This article is published with open access at Springerlink.com
Abstract
Purpose Human DNA topoisomerases I and II (topo-I
and -II) are essential for vital cellular processes such as
DNA replication, transcription, translation, recombination,
and repair. In the present study, we correlate topo-I and -II
expression and outcome after chemotherapy in primary and
relapsed colorectal cancer.
Patients and methods Patients with colorectal cancer that
had recurred, following surgery and adjuvant chemotherapy
and underwent a second operation were included in the
present study. All had undergone surgical resection of the
primary tumor and received post-operatively 5-FU-based
(5FU + Leucovorin, Mayo Clinic regimen) adjuvant che-
motherapy. Tumor tissue was collected at the initial opera-
tion from the primary tumor and at the time of recurrence
(during the second operation following chemotherapy). All
tissue samples were analyzed for levels of expression of
both topo-I and topo-IIa using standard three-step immuno-
histochemistry on paraYn sections.
Results Forty patients were included. Levels of expres-
sion of topo-I and topo-II were higher in malignant cells
from tumor recurrences compared to primary tumors
(P = 0.0001 for both). There was a statistically signiWcant
positive relationship between patients age and levels of
topo-I (P = 0.011) and topo-II (P = 0.011) expression.
Conclusions The study results reported here underscore
the role of topoisomerase expression in colorectal cancer
and suggest a potential role in tumor recurrence.
Keywords Topoisomerase I · Topoisomerase II ·
Colorectal cancer · 5-FU · Chemotherapy
Introduction
The aim of the present study was to investigate whether
chemotherapy with 5-FU alters the levels of topoisomerase
I (topo-I) and II (topo-II) in neoplastic tissues from patients
with colorectal cancer. To this end, we examined the rela-
tionship between clinical data and the expression of topo I
and II in patients treated with 5-FU post-operatively and
who underwent surgery at recurrence.
Human DNA topo-I is an essential nuclear enzyme for
vital cellular processes such as DNA replication, transcrip-
tion, translation, recombination and repair. Topo-I unwinds
and uncoils the supercoiled DNA double helix by transiently
cleaving one of the two strands and allowing its rotation
over the other, following which topo-I reseals the cleaved
strand [1–5]. Topo-II works in a similar manner, with the
diVerence that it cleaves both DNA strands, allowing the
passage of an intact double helix through the break. The
entire reaction takes place at the expense of ATP hydrolysis
[6]. In contrast to topo-I, which is monomeric, two homolo-
gous but distinct isoforms of type II human topoisomerases
N. Tsavaris (&) · P. Gouveris · P. Kopterides
Medical Oncology Unit, Department of Pathophysiology,
Medical School, “Laikon” University General Hospital,
National and Kapodistrian University of Athens,
Athens University School of Medicine, 11527 Athens, Greece
e-mail: tsavari1@otenet.gr
A. Lazaris · N. Kavantzas · T. Papathomas · G. Arapogiannis ·
H. Zorzos · V. Kyriakou · E. Patsouris
First Department of Pathology, Medical School,
“Laikon” University General Hospital, National and Kapodistrian
University of Athens, Athens, Greece
C. Kosmas
Second Department of Medical Oncology,
“Metaxa” Cancer Hospital, Piraeus, Greece
e-mail: ckosm1@ath.forthnet.gr