P0069 Molecular markers of prognosis and individualisation of colon cancer treatment

Abstract

Background Disease stage and degree of tumour differentiation are the main parameters determining treatment approach and prognosis in colon cancer. However, even within a clinically homogeneous group of patients with colon cancer, some diversity will arise due to differing molecular pathogenesis. This study examines molecular and genetic parameters of disease in patients with locally advanced colorectal cancer. Methods We analysed clinical data for 16 patients with T4N0−1M0 stage locally advanced colorectal cancer (LACC), treated in the department of coloproctology and chemotherapy between 2012 and 2013. Immunohistochemical study and analysis of blood were done for the detection of tumour markers BRCA1 and TOP2A and for oestrogen and progesterone receptor status. Findings The mean age of the patients was 49.4 ± 3.6 years. Analysis of the expression of BRCA1 and TOP2A as predictive markers of sensitivity and resistance to chemotherapy was performed in all 16 patients. High expression of BRCA1 and TOP2A was found in ten and eight patients, respectively. Low expression of these markers was detected in six and eight patients, respectively. Of 16 patients, six (38%) had the hormone-sensitive form of colon cancer and underwent chemotherapy with the FOLFOX plus tamoxifen regimen. Patients with hormone negative cancer received FOLFOX without tamoxifen. After treatment, nine (56%) of the 16 patients had at least partial tumour regression, in the remaining seven (44%) the disease was stabilised. Interpretation These data show pronounced heterogeneity in expression of molecular biomarkers in LACC, which will result in differing sensitivity to drug therapies. The findings suggest the need for further study of the expression of markers BRCA1 and TOP2A, the presence of these mutations, and oestrogen and progesterone receptor status to identify predictors of the efficacy of drug therapy in patients with locally advanced colorectal cancer. Disease stage and degree of tumour differentiation are the main parameters determining treatment approach and prognosis in colon cancer. However, even within a clinically homogeneous group of patients with colon cancer, some diversity will arise due to differing molecular pathogenesis. This study examines molecular and genetic parameters of disease in patients with locally advanced colorectal cancer. We analysed clinical data for 16 patients with T4N0−1M0 stage locally advanced colorectal cancer (LACC), treated in the department of coloproctology and chemotherapy between 2012 and 2013. Immunohistochemical study and analysis of blood were done for the detection of tumour markers BRCA1 and TOP2A and for oestrogen and progesterone receptor status. The mean age of the patients was 49.4 ± 3.6 years. Analysis of the expression of BRCA1 and TOP2A as predictive markers of sensitivity and resistance to chemotherapy was performed in all 16 patients. High expression of BRCA1 and TOP2A was found in ten and eight patients, respectively. Low expression of these markers was detected in six and eight patients, respectively. Of 16 patients, six (38%) had the hormone-sensitive form of colon cancer and underwent chemotherapy with the FOLFOX plus tamoxifen regimen. Patients with hormone negative cancer received FOLFOX without tamoxifen. After treatment, nine (56%) of the 16 patients had at least partial tumour regression, in the remaining seven (44%) the disease was stabilised. These data show pronounced heterogeneity in expression of molecular biomarkers in LACC, which will result in differing sensitivity to drug therapies. The findings suggest the need for further study of the expression of markers BRCA1 and TOP2A, the presence of these mutations, and oestrogen and progesterone receptor status to identify predictors of the efficacy of drug therapy in patients with locally advanced colorectal cancer.