DETECTION AND PROGNOSIS OF GASTROINTESTINAL CANCER

University Of Minnesota Twin Cities, Minneapolis MN

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Abstract

Colon cancer is the second leading fatal malignancy in the United States. Prognosis and patient selection for adjuvant chemotherapy are determined by pathological and clinical staging. Previous studies have shown that colon cancer patients with lymph node metastases will benefit from chemotherapy following surgical treatment of their cancer. Survival of patients with early stage colon cancer is generally good, but a subgroup of up to 25-30 percent will relapse. Currently it is difficult to determine which patients will relapse. Characteristics of the primary tumor, such as chromosome 18q deletion or expression of sialylated carbohydrate antigens may predict subsequent prognosis, however few prospective studies exist that demonstrate the clinical utility of these markers. The applicants hypothesize that poor survival in some patients with early stage colon cancer is due to the presence of occult micrometastases at the time of surgery. A method for the detection of micrometastases in histologically-negative lymph nodes using a polymerase chain reaction-based assay for one mucin type glycoprotein (MUC2) has been developed. Mucins are large glycoproteins that are highly expressed in the normal colon and in primary colon cancers. Preliminary data using this assay indicates that MUC2-positive cancer cell micrometastases can be detected in histologically-negative lymph nodes from 14 or 42 (32.5 percent) early stage colorectal cancer patients. The presence of these micrometastases correlates with greater depth of invasion of the primary tumor. In contrast, MUC2-positive cells were detected in 42/43 (98 percent) of primary cancers and were never detected in the lymph nodes from 6 patients with non-malignant colon disease. The purpose of this study is to determine if the presence of MUC2-positive micrometastases will predict which stage II colon cancer patients will have a cancer relapse or predict overall survival. A secondary purpose is to compare the sensitivity and specificity of immunohistochemical techniques to detect lymph node micrometastases and to determine the accuracy of other prognostic markers (chromosome 18q deletion and sialylated carbohydrate molecules) in this group of early stage cancers. These studies will potentially enable clinicians to more effectively identify patients with early stage colon cancer who would benefit from adjuvant therapies.