Prognostic factors in colorectal cancer

Colorectal cancer (CRC), the most common gastrointestinal cancer, causes around 2500 deaths annually in Sweden. Tumour resection is still the only curative treatment, but surgery is successful in only about half of the patients. The best prognostic factor so far is the tumour stage according to the TNM classification system which is based on the perioperative findings of the extent of the tumour growth. Adjuvant chemotherapy has been shown to reduce the number of deaths with about one third in the selected group of patients with metastatic disease in the regional lymph nodes. Among patients having surgery for tumours in more favourable stages, still some will die from cancer that might have been cured by adjuvant chemotherapy. We have therefore looked for better prognostic factors to improve the selection of patients for adjuvant chemotherapy treatment. In our first paper, we analysed the prognostic impact of immunohistologic detection with cytokeratin 8/18 of disseminated tumour cells in regional lymph nodes among 147 patients without any detected tumour cells at routine examination. We observed tumour cells in lymph nodes from 32% of the patients, but their presence had no prognostic impact on survival. In the next study, we evaluated preoperative serum levels of the metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2, and we found elevated levels in cancer patients compared to healthy controls. However, large overlapping ranges between serum levels in patients and controls reduced the clinical benefit of the test. In paper three, we studied the metastatic tissue in lymph nodes from 93 patients regarding the number of immune cells showing positivity for CD8, CD45R0 and CD68. High numbers of these immune cells correlated to a favourable prognosis. In paper four, we developed a method using real-time quantitative RT-PCR for detection of CEA mRNA in regional lymph nodes with microscopically normal appearance as a marker for disseminated tumour cells. Quantitative RT-PCR presented as a highly sensitive and specific method. The clinical impact of detected CEA mRNA in lymph nodes according to survival remains to be evaluated in further studies. In summary, our studies aimed to identify methods for improved tumour staging in CRC indicate, that real-time quantitative RT-PCR for CEA seems to be a more sensitive method than immunohistologic detection of CEA-positive cells for early detection of disseminated disease in the regional lymph nodes.