Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer

A significant number of patients with liver metastases from colorectal canc er (CRC) achieve 5-year survival after liver resection. Increased expressio n of genetic markers in the primary tumor are known to predict outcome afte r colonic resection, but the predictive value of such markers after resecti on of hepatic metastases is unknown. The objective of this study was to eva luate whether DNA content and multiple genetic markers, separately or expre ssed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liv er tissue of 71 consecutive patients who had undergone a potentially curati ve resection of hepatic metastases from CRC. Using DNA flow cytometry and i mmunohistochemical staining techniques we determined the DNA content and th e level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p 53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, ca ncer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlatio n detected between the DNA aneuploidy and overall or cancer-specific surviv al. Similarly, expression of the individual tumor-associated proteins did n ot predict survival. Patients whose tumors co-expressed multiple markers ha d survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-p ositive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that th e DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of he patic metastases from CRC. However, the immunoreactivity of p53 may be an i mportant marker of local recurrence in the liver, which may be useful if re -resection of metastatic liver tumors is considered a viable management opt ion in this disease.