TOP1 gene copy number and TOP1/CEN-20 ratio in stage III colorectal cancer samples

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AIM OF STUDY
To investigate if TOP1 gene copy number and/or the TOP1/CEN-20 ratio in colorectal cancer (CRC) areassociated with prognosis.
BACKGROUND
TOP1, localized on chromosome 20, encodes topoisomerase I (TOP1), which is the sole molecular target of irinotecan. TOP1 immunoreactivity in formalin fixed paraffin embedded (FFPE) primary tumor tissue has been suggested as a predictive biomarker of the effect of irinotecan in the treatment of metastatic CRC. Quantification of TOP1 protein levels in FFPE tissue may be difficult and calls for alternative methods.We have recently reported on TOP1 FISH analyses on 50 FFPE primary CRC tissues. When compared with results from normal colorectal mucosa, 80 % of the tumors showed increased TOP1 gene copy number and 2/3 had increased TOP1/CEN-20 ratio.
MATERIALS AND METHODS
FFPE samples from 154 stage III CRC patients not receiving adjuvant chemotherapy were included. For each patient TOP1 gene copy number and CEN-20 reference number were determined in 60 nuclei from the malignant tumor by FISH using a TOP1/CEN-20 probe mix. Similarly, the TOP1 gene copy number and and CEN-20 reference number were dertermined in the normal colorectal mucosa in 105 of the 154 patients.
RESULTS
We found that: 84 % of the tumors to have increased TOP1 gene copy number/cell. 68 % of the tumors to have increased TOP1/CEN-20 ratio. 23 % of the tumors to have TOP1/CEN-20 ratio above 1.5. 10 % of the tumors to have TOP1/CEN-20 ratio above 2.0. A continuous relationship between TOP1 gene copy number/cell and OS exists. A continuous relationship between TOP1 gene copy number/cell and LR exists. A continuous relationship exists between TOP1/CEN-20 ratio and LR
CONCLUSION
Our data suggest that TOP1 and TOP1/CEN-20 ratio are associated with prognosis in colorectal cancer. Future studies investigating a potential predictive role of TOP1 gene status as a biomarker for irinotecan sensitivity should be planned in a way so the prognostic and the predictive values can be separated.
Original languageEnglish
Publication date27 Apr 2012
Publication statusPublished - 27 Apr 2012
EventDansk Selskab for Cancerforsknings årsmøde 2012 - Vilvorde, Ordrup, Denmark
Duration: 27 Apr 201227 Apr 2012

Conference

ConferenceDansk Selskab for Cancerforsknings årsmøde 2012
LocationVilvorde
CountryDenmark
CityOrdrup
Period27/04/201227/04/2012

ID: 40514574