Μελέτη της μοριακής έκφρασης της κυκλοοξυγενάσης (COX-2) και της διυδροπυριμιδινικής δεϋδρογενάσης (DPD) σε ασθενείς με εξαιρέσιμο ορθοκολικό καρκίνο ; Evaluation of cyclooxygenase (COX-2) and dihydropyrimidine dehydrogenase (DPD) expression in resectable colorectal carcinoma

The aim of this thesis was to study using methods of molecular biology and immunohistochemical techniques, the expression of cyclooxygenase (COX-2) and dihydropyrimidine dehydrogenase (DPD) and the potential prognostic and predictive significance in patients’ tumors that underwent surgery for resectable colorectal cancer without metastatic disease (Stage I-III). The study included 96 patients with colorectal cancer, from which 59 patients (61.5%) received adjuvant chemotherapy. With a median follow-up of 82.7 months (range 82.7-95.2), 21 relapses (21.9%) and 30 deaths (31.2%) were recorded. The analyzes of the clinicopathological characteristics of patients and disease-free survival (DFS), showed statistically significant correlation with the presence of lymph node invasion (N), histological differentiation (Grade) and stage of disease (AJCC). The analysis of the clinicopathological characteristics of patients and overall survival (OS) highlighted a statistically significant correlation of survival only with age and histological differentiation (Grade). It was also demonstrated a statistically significant association between chemotherapy and overall survival, but not between chemotherapy with disease free survival. In 85 (89%) of these patients’ tumors the expression of COX-2 protein studied by immunohistochemistry using monoclonal antibody on tissue microarrays, while in 84 (88%) tumors the gene expression of mRNA of DPYD and PTGS2 was also investigated using qRT-PCR. Immunohistochemical analysis revealed that high protein expression levels for COX-2 were found in 69.4% of the tumors. Our results show that immunohistochemically assessed COX-2 protein expression levels, as well as mRNA expression levels of DPYD and PTGS2 had no independent prognostic significance for OS and DFS in the colorectal cancer patient’s cohort studied. No statistically significant association was also found for age, gender, primary site, T-stage, lymph nodes status, tumor grade, tumor stage (AJCC) and chemotherapy correlated with all ...