scholarly journals PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chenbo Zhang ◽  
Ajian Li ◽  
Huaguang Li ◽  
Kangsheng Peng ◽  
Qing Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcomes ◽  
Copy Number ◽  
Gene Copy Number ◽  
Tumor Location ◽  
Stage Iii ◽  
Gene Copy ◽  
Tissue Samples ◽  
Relative Copy Number ◽  
Colorectal Cancer Patients

Aim. To investigate the correlation between PPP1R12A gene copy number and clinical outcomes of oxaliplatin-based regimen in stage III colorectal cancer (CRC).Methods. A total of 139 paraffin-embedded tissue samples of stage III CRC patients who received oxaliplatin-based treatment after radical surgery were recruited. Genomic DNA was extracted and purified from paraffin-embedded sections. Quantitative PCR methods were used to detect the relative copy number (RCN) of PPP1R12A.Results. Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR=2.186, 95% CI: 1.293–3.696;P=0.003) and OS (HR=2.782, 95% CI: 1.531–5.052;P<0.001). Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIBHR=2.870,P<0.001; colonHR=1.910,P=0.037; OS: IIIBHR=3.527,P<0.001; IIICHR=2.662,P=0.049; rectumHR=4.229,P=0.002).Conclusion. Our findings suggest the copy number of PPP1R12A can independently predict recurrence and overall survival of stage III colorectal cancer patients receiving oxaliplatin-based chemotherapy.

scholarly journals Topoisomerase 1(TOP1 ) gene copy number in stage III colorectal cancer patients and its relation to prognosis

2012 ◽  
Vol 7 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Maria Unni Rømer ◽  
Sune Boris Nygård ◽  
Ib Jarle Christensen ◽  
Signe Lykke Nielsen ◽  
Kirsten Vang Nielsen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Gene Copy Number ◽  
Stage Iii ◽  
Gene Copy ◽  
Topoisomerase 1 ◽  
Colorectal Cancer Patients

Epidermal growth factor gene amplification is not frequent and cannot account for antitumor activity of cetuximab plus chemotherapy in advanced colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3561-3561 ◽  
Author(s):  
C. Garufi ◽  
M. Mottolese ◽  
A. Cianciulli ◽  
M. Zeuli ◽  
S. Buglioni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Cancer Patients ◽  
Copy Number ◽  
Advanced Colorectal Cancer ◽  
Gene Copy Number ◽  
Chromosome 7 ◽  
Gene Copy ◽  
Egfr Gene ◽  
Colorectal Cancer Patients

3561 Cetuximab has been shown to be active in the metastatic colorectal cancer, but EGFR detection by immunohistochemistry is not predictive for tumor response. Moroni et al (Lancet Oncology 2005) showed that, in patients responsive to Cetuximab, EGFR gene copy number, assessed by FISH, was increased. On this basis, copy number and protein status of EGFR were investigated in 70 primary and/or metastatic colorectal carcinomas. Protein expression was assessed by immunohistochemistry (IHC) using DAKO EGFRPharmDX kit. Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Dual-target, dual-color FISH assays were performed using the LSI EGFR SpectrumOrange/CEP 7 Spectrum Green probe. EGFR gene copy number, chromosome 7 copy number and the average EGFR gene to chromosome 7 signal ratio were reported as FISH genetic variables. Chromosome 7 was polysomic when cancer cells showed multiple centromere signals: low polysomy (2 to 5 signals), high polysomy (>5 signals). Samples with a ratio value ≥ 2.0 were considered to be amplified. EGFR protein was overexpressed in 57 out of 70 patients (81%). In the group of 58 patients evaluated as polysomic, 48 (82,7%) had a low polysomy level, whereas 20 (12.7%) had a high polysomy level. Gene amplification was seen only in 3/70 patients. High polysomy was evidenced only in the group of patients displaying an EGFR IHC score 2+/3+. Forty-six pretreated patients received a cetuximab-based treatment. Response to treatment has been already evaluated in 26 FISH-negative patients while for the other 20 it is still too early. We observed 7 PR (27%), 9 SD (35%) and 10 PD (38%). This study shows that in this series of advanced colorectal cancer patients, EGFR amplification, measured by FISH, is a rare event (4%) and could be considered together with chromosome 7 polysomy for the antitumor activity. No significant financial relationships to disclose.

TOP1 gene copy number in stage III colorectal cancer (CRC) samples: Association to prognosis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 475-475
Author(s):  
Sune Boris Nygaard ◽  
Maria Unni Rømer ◽  
Ib Jarle Christensen ◽  
Signe Lykke Nielsen ◽  
David Hersi Smith ◽  
...  
Keyword(s):  
Predictive Value ◽  
Copy Number ◽  
Gene Copy Number ◽  
Tumor Location ◽  
Response To Therapy ◽  
Stage Iii ◽  
Gene Copy ◽  
Continuous Variables ◽  
Future Studies ◽  
Significant Difference

475 Background: TOP1 inhibitor treatment is frequently being used in combination therapy of metastatic CRC. This study aims to reveal whether TOP1 gene copy number associates with patient prognosis, since such a relationship may have significant implications for future studies aiming at validating the predictive value of TOP1 gene copy number. Methods: The study included TOP1 and CEN-20 FISH analyses (DAKO A/S Denmark) on FFPE tissue sections from 154 stage III CRC patients who did not receive adjuvant chemotherapy. TOP1 gene copy number, CEN-20 copy number and the TOP1/CEN-20 ratios were analyzed and correlated to overall survival (OS), to time to recurrence (TTR) of patients with CRC and to local recurrence (LR) in patients with rectal cancer (RC). Results: TOP1 copy number counts and the TOP1/CEN-20 ratios, age, gender and primary tumor location were separately added into a multivariate analysis as continuous variables. For OS and LR, TOP1 copy number was significant and the ratio was borderline significant with higher copy number associated with longer OS or longer time to LR. When the patients were dichotomized using the TOP1 median copy number, we found that patients with high TOP1 copy number in their tumor cells had a significant longer OS (HR: 0.68; 95% CI: 0.47-0.98; p = 0.04) compared to patients with low TOP1 copy number. Using the median TOP1/CEN-20 ratio to dichotomize, no significant differences were observed between patients with levels above or below the median ratio number for OS (HR: 0.76; 95% CI: 0.53-1.10; p = 0.14). TOP1 copy number divided the RC patients into two groups with a trend towards a significant difference in time to LR (HR: 0.56; 95% CI: 0.27-1.16; p = 0.11) with higher copy number. If the median ratio was used, a significant association with longer time to LR (HR: 0.43; 95% CI: 0.20-0.92; p = 0.03) was found. No significant associations between TOP1 copy number or ratio and TTR were observed. Conclusions: Increased TOP1 copy number is associated with longer OS in CRC patients and fewer LR in RC patients. Thus, future studies analyzing the association between TOP1 copy number and response to therapy in CRC patients should be planned in such a way that a prognostic and a predictive value of TOP1 can be separated.

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