Search

Background: Several studies have recently indicated the prognostic or predictive role of several biomarkers in colorectal cancer. We sought to investigate the prognostic value of prostaglandin synthase 2 (PTGS2), cyclooxygenase 2 (COX2), thymidylate synthetase (TYMS), thymidine phosphorylase (TYMP), dihydropyrimidine dehydrogenase (DPYD) and topoisomerase I (TOPO1) in colorectal cancer patients treated with 5-FU-based regimens, such as De Gramont and FOLFOX in the adjuvant setting., Materials and Methods: In total, 96 formalin-fixed paraffin-embedded and 30 fresh-frozen tumor tissue samples were evaluated using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction and microarray gene expression profiling, respectively., Results: The majority of tumors exhibited protein overexpression of COX2 (69%), TYMS (75%) and TOPO1 (75%). There was a significant association of TYMP protein expression with T classification, gender and stage (p=0.040, p=0.041 and p=0.011, respectively). TOPO1 protein expression was correlated with TOPO1 mRNA expression and was positively associated with stage (p=0.002) and lymph node infiltration (p=0.004). In univariate analysis, patients with high TYMS mRNA expression were shown to have a significantly lower risk for progression and death (Wald's p=0.030 and p=0.015, respectively). However, in multivariate analysis, only a trend for decreased risk for death was shown in patients with high TYMS mRNA expression (Wald's p=0.083), while patients with high PTGS2 mRNA expression had a trend for lower risk for progression (p=0.064). Using supervised hierarchical clustering, based on the expression in fresh-frozen tumor tissue of PTGS2, TYMS, TYMP and DPYD, our 30 patients were separated into two clusters. One of the clusters was enriched with patients with infiltrated lymph nodes (p<0.05), suggesting that these genes might have an impact on the tumor's ability to metastasize., Conclusion: These findings indicate a possible prognostic role of TYMS mRNA expression and highlight a cluster of genes associated with nodal metastases that warrant further investigation in a larger cohort of patients with colorectal cancer treated with 5-FU-based adjuvant chemotherapy., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Although Kirsten rat sarcoma (KRAS) gene mutational testing is essential for the optimal design of therapeutic strategies for colorectal cancer, it is not always feasible or reliable. In this retrospective study, we examined whether (18)F-Fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans can serve as a surrogate examination for KRAS mutational testing., Patients and Methods: KRAS codon 12 and 13 mutational status was tested in 44 colorectal primary tumors and was compared with the (18)F-FDG PET/CT maximum standardized uptake value (SUVmax) values of the respective metastatic lesions. Glucose transporter-1 (GLUT1) mRNA levels were also measured in colorectal primary tumors., Results: No statistically significant correlation between (18)F-FDG PET/CT SUVmax values and KRAS mutation status was found (parametric t-test: p=0.4753; non-parametric Kruskal-Wallis test: p=0.51). This result cannot be attributed to the effect of differing GLUT1 mRNA levels, as shown by multivariate analysis., Conclusion: Our study failed to promote (18)F-FDG PET/CT uptake as a surrogate examination for KRAS mutation testing.

Background: This study reports the long-term follow-up of patients with metastatic colorectal cancer (CRC) participating in a randomised phase II study that compared the efficacy and toxicity of the combination of irinotecan (IRI), fluorouracil (FU) with leucovorin (LV) (arm A) versus sequential chemotherapy with IRI plus FU/LV followed by oxaliplatin (OXA) plus FU/LV (arm B) as first line therapy., Materials and Methods: Intent-to-treat analysis was performed on 417 patients (211 in arm A and 206 in arm B). Treatment schedules of weekly IRI 80 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) immediately followed by intravenous bolus FU 450 mg/m(2) for 6 weeks were followed by a 2-week rest period. Treatment continued for 4 cycles. Patients in arm A were treated with IRI/FU/LV for 4 cycles, while patients in arm B were initially treated with IRI/FU/LV for 2 cycles followed by sequential administration of 2 cycles of OXA/FU/LV., Results: No significant difference emerged in overall response rate or overall survival. There was a difference in progression-free survival (median, 7.3 versus 8.2 months, p=0.040) in favour of arm B. Toxicity profiles were similar in both arms., Conclusion: IRI/FU/LV and IRI/FU/LV followed by OXA/FU/LV showed comparable activity with a manageable toxicity profile.