Adverse outcome in patients who undergo curative surgical resection of rectal and colonic carcinoma results from local recurrence or emergence of initially occult distant metastases. Molecular methodologies offer new approaches to evaluate the status of resection margins and the metastatic phenotype in primary tumors. Polymerase chain reaction with cloning into bacteriophage vectors for further expansion permits detection of DNA from one mutant cancer cell among thousands of non-neoplastic cells. Representational difference analysis (RDA) provides the ability to identify and characterize amplifications which may be prognostic markers in tumors. The hypotheses to be tested in this project are: l. Microscopically occult neoplastic cells at the surgical margins of rectal cancer patients can be detected by molecular genetic analysis, thereby serving as markers for recurrence. 2. Amplified genes in primary colorectal carcinomas are markers for poor prognosis.
Our specific aims for this project are to: l. Evaluate mutations in ras and p53 genes in margin tissue and pelvic irrigation specimens collected after curative resection of rectal carcinomas. Molecular genetic results will be related to histopathologic findings, recurrence, and survival. 2. Apply representational difference analysis (RDA) to pairs of matched metastatic and non-metastatic primary colorectal carcinomas. RDA probes detecting amplifications will be cloned, mapped, and used to search for target genes. The amplifications will be evaluated as prognostic markers.
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