ALLELIC IMBALANCE AND MICROSATELLITE INSTABILITY IN RESECTED DUKE D COLORECTAL-CANCER

Hepatic resection is the treatment of choice for selected patients wit h liver metastases from colorectal cancer (CRC). Although the 5-year s urvival rate among patients after liver resection is 25-45%, 55-75% of patients die from progressive disease. The purpose of this study was to characterize molecular genetic alterations, including microsatellit e instability and allelic imbalance, in patients with potentially cura tive resected liver metastases from CRC and to correlate these molecul ar features with clinical and pathologic characteristics. We examined DNA from formalin-fixed, paraffin-embedded archival tumor specimens fr om 141 surgically resected hepatic metastases from CRC. We used micros atellite markers localized to chromosome arms 5q, 8p, 10q, 15q, 17p, 1 8p, and 18q in a polymerase chain reaction-based assay. Allelic imbala nce at each locus and the presence of tumor microsatellite instability were correlated with clinicopathologic features of the tumor and clin ical course of the patient. Microsatellite instability at multiple loc i was seen in only 2.5% of resected liver metastases, a frequency sign ificantly lower than that previously detected for primary CRC. Additio nally, these findings had no significant correlation with disease-free survival or overall survival. Allelic imbalance at one or more loci w as seen in 87% of informative tumors. Allelic imbalance on chromosome 17p was seen in 84% of informative tumors, and its presence was associ ated with a significantly poor disease-free survival (p = 0.015) and o verall survival (p = 0.05). These data suggest that allelic imbalance on chromosome 17p is an independent prognostic parameter in patients w ith potentially curative resected liver metastases from CRC. Such alte rations could provide a useful stratification criterion for adjuvant t herapy for patients who have undergone curative resection of liver met astases from CRC.