Biological prospectives to define prognosis and treatment strategies in liver metastases from colorectal cancer.

Liver metastases arise in about a third of patients with colorectal cancer. Although important clinical results have been obtained by surgical treatment in patients with limited liver involvement, other intra-arterial or systemic therapies do not provide important long term clinical benefits in patients with unresectable liver metastases. Better knowledge of the biology of liver metastases could imply a more appropriate use of the available therapeutic approaches and a retrospective definition the biologic subgroups of patients who benefit from them. Phenotypic and molecular aspects of tumor cells have been investigated and have proven to be important determinants of clinical outcome in patients with different human tumor types. Liver metastases from colorectal cancer have been scarcely studied, but cell proliferation has been shown to be a discriminant of freedom from progression and even more of long-term clinical outcome in subsets in patients treated with radical surgery. Moreover, in patients with resectable liver metastases, DNA and entity of DNA abnormalities are significantly associated with patient survival. A few recent reports have indicated a potential prognostic relevance of abnormal activation or expression of the p53 tumor suppressor gene, bel-2 protein and ras oncogene. In conclusion, prognostic biologic factors are acquiring an important role as indicators of clinical outcome in patients with liver metastases. However, all information is derived from retrospective analyses heterogeneous for patient population and biomarkers analyzed. Therefore, the comparison among results from different studies is difficult, and prospective studies are needed to develop a prognostic classification which integrates biologic and pathologic factors.