Topoisomerase I and IIalpha protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy.
OBJECTIVE
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.


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 chemotherapy. Tumor tissue was collected at the initial operation 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 immunohistochemistry on paraffin sections.


RESULTS
Forty patients were included. Levels of expression 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 significant 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.
Tsavaris
Nicolas
N
Medical Oncology Unit, Department of Pathophysiology, Medical School, Laikon University General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece, tsavari1@otenet.gr
Lazaris
Andreas
A
Kosmas
Christos
C
Gouveris
Panagiotis
P
Kavantzas
Nikolaos
N
Kopterides
Petros
P
Papathomas
Thomas
T
Agrogiannis
George
G
Arapogiannis
George
G
Zorzos
Haralambos
H
Kyriakou
Vassiliki
V
Patsouris
Efstratios
E
Patsouris
Efstathios
E
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D003131:Combined Modality Therapy; D004247:DNA / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D005472:Fluorouracil