APOPTOSIS AND %S AS PROGNOSTIC FACTORS FOR COLON CANCER

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The growth of a colon cancer is determined by the rates of malignant cell proliferation and natural apoptosis. Because of molecular genetic changes in the cancer cell both of these processes can be disrupted and lead to tumor growth. We hypothesize that the rate of colon cancer cell apoptosis is an important determinant of net cancer cell growth and that a measure of the percent cells in apoptosis will provide additional prognostic information to the cell proliferation rate. The overall goals of this proposal are to measure the rates of basal apoptosis and cell proliferation on specimens of colon adenocarcinomas and relate these measurements to prognosis and the molecular genetic abnormalities determined on the same tumor sample. Paraffin-embedded tissue from patients that participated in randomized, controlled NCCTG clinical trials which now have adequate follow-up data to correlate these measurements to colon cancer recurrence and survival. Cell proliferation and DNA ploidy will be measured using state-of-the-art flow cytometry hardware and software. Apoptosis will be measured with a TUNEL technique. We propose to utilize the cell proliferation (percent S and percent G2M phases) and percent apoptosis measurements to develop a formula - the colon cancer growth index (CCGI) - that better predicts prognosis. The second hypothesis to be tested is that the alterations of cancer cell proliferation and apoptosis are the consequences of genetic abnormalities and that these genetic abnormalities will differentially affect proliferation and apoptosis. This study offers the unique opportunity to study the cell proliferation and apoptosis rates of colon cancers that have already been studied for molecular abnormalities by Dr. Steven Thibodeau in a previous study (NCCTG 93-46-55). By performing these assays on clinical material, we aim to translate these findings into prognostic tools that can be used in the clinic to formulate new treatment strategies based on the knowledge of apoptosis and cell proliferation of colon cancers.