Topoisomerase I expression correlates to response to neoadjuvant irinotecan-based chemoradiation in rectal cancer.
Biomarkers may help predict the efficacy of neoadjuvant chemoradiation in patients with rectal cancer. We hypothesized that the expression of topoisomerase I (Topo I) and thymidylate synthase (TS) may help predict the treatment response in patients undergoing irinotecan and capecitabine-based chemoradiation. Patients with rectal cancer (cT3/4Nx or Tx/N+) received neoadjuvant chemoradiotherapy within clinical studies with irinotecan and capecitabine. Samples of normal and tumour tissues were collected before the start of the treatment and during surgical resection. Topo I and TS were measured using real-time PCR. The results of gene expression levels were compared between responders (defined as ypT0-2 ypN0) and nonresponders (ypT3-4 or ypN1/2). A total of 38 patients were analysed, 18 of them were responders. The biopsies of the untreated tumour tissue of responding patients showed a significant higher expression of Topo I compared with nonresponding patients (P = 0.015). Normal tissue did not show this difference (P = 0.126). During chemoradiation, the Topo I expression in tumour tissue of responders decreased significantly. TS did not show any differences between responders and nonresponders before treatment, but a significant decrease in the tumour tissue of responders was noted at the end of the treatment. Our data suggest that Topo I expression in rectal tumour mucosa might serve as a predictor of response to the neoadjuvant irinotecan-based chemoradiation, and hence might be a factor contributing to the development of individualized treatment.
Chirurgische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany. k.horisberger@gmx.de
Karoline
K
Horisberger
Philipp
P
Erben
Benjamin
B
Muessle
Christoph
C
Woernle
Philipp
P
Stroebel
Georg
G
Kaehler
Frederik
F
Wenz
Andreas
A
Hochhaus
Stefan
S
Post
Frank
F
Willeke
Ralf-Dieter
RD
Hofheinz
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000077146:Irinotecan; D020360:Neoadjuvant Therapy / Q000379:methods; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D000077146:Irinotecan; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin