Biochemical and Clinical Approaches in Evaluating the Prognosis of Colon Cancer

Background: Colorectal adenocarcinoma is a common malignant neoplasm in the Western world. To achieve optimal treatment results, the risk estimation of recurrence should be as accurate as possible. Materials and Methods: Tissue material from tumour and normal mucosa was taken from six patients and was analysed to screen aberrantly expressed genes using cDNA microarray. Selected up-regulated genes were chosen for further analysis by immunohistochemistry. For this purpose a tissue array material of 114 colorectal cancer patients was obtained. In addition to the routinely used proliferation marker Ki-67, the analysed proteins included securin and CDC25B. Results: Processes such as cellular defense, cell structure, motility and cell division were found to be notably represented among the most deregulated genes. A significant portion of the overexpressed genes included those functioning in the cell cycle. Immunohistochemical stainings of securin and CDC25B showed a consistent expression pattern with that of cDNA microarray analysis. There was no statistical association between the studied proliferation markers and survival. Instead, there was a significant association between the Dukes' class and the histological grade (p=0.04), but not between histological grade and survival. The survival of Dukes' B patients was significantly poorer if no regional lymph nodes were studied compared with the Dukes' B patients with even a single lymph node was studied (p=0.04, hazard ratio 2.7). Conclusion: Tumour stage is superior in estimating the prognosis of patients with colonic cancer compared with the grading of cell cycle regulators or histological grade of the cancer. The study of regional lymph nodes is essential to identify the patients who would benefit from adjuvant chemotherapy. Colorectal cancer is one of the most common malignant neoplasms in the Western world. During the last years the prognosis has improved due to improvements in diagnostics, surgery and oncology. The prognosis in stage I colon cancer (Dukes' A) is excellent and no additional treatment is needed after surgery. The challenge is the treatment of stage II-III (Dukes' B-C) colon cancer patients, whose prognosis can be improved by adjuvant treatments (1, 2). The prediction of treatment efficacy in disseminated disease (stage IV) would also be beneficial. The markers that may predict the efficacy of chemotherapy have been identified (3). However, new prognostic factors would be helpful to focus the intensive adjuvant chemotherapy on high-risk patients. Microarray techniques have yielded promising results in developing new treatments and the estimation of prognosis in some tumours (4, 5), for instance in haematological malignancies (5). In this study, cDNA microarray was used as a screening method in a small group of colon cancer patients to identify up- and down-regulated genes. Selected up-regulated genes involved in cell cycle regulation were chosen for further analyses. The association between their expression level and survival of colon cancer patients was studied in a tissue array material of 114 colon cancer patients using immunohistochemistry. In addition, clinical and routine histological characteristics of these patients were analysed.