Abstract
Background:
Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and
functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have
previously been implicated in resistance to platinum compounds. The aim of the current investigation is to
determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in
colorectal cancer (CRC).
Methods:
Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probes
were constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRC
chemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time to
recurrence, and local recurrence in rectal cancer) were analyzed by survival statistics.
Results:
ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patient
material, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens,
whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain was
significantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patients
with colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients.
Conclusions:
ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patients
with colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treated
patient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC.
Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and
functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have
previously been implicated in resistance to platinum compounds. The aim of the current investigation is to
determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in
colorectal cancer (CRC).
Methods:
Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probes
were constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRC
chemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time to
recurrence, and local recurrence in rectal cancer) were analyzed by survival statistics.
Results:
ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patient
material, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens,
whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain was
significantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patients
with colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients.
Conclusions:
ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patients
with colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treated
patient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 13:489 |
| Tidsskrift | BMC Cancer |
| Vol/bind | 13 |
| Antal sider | 10 |
| ISSN | 1471-2407 |
| DOI | |
| Status | Udgivet - 21 okt. 2013 |
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