Rb, mcl-1 and p53 expression correlate with clinical outcome in patients with?liver metastases from colorectal cancer

Background:Thymidylate synthase (TS) has been associatedwith clinical outcome in disseminated colorectal cancer. However, manypatients with low TS expression still fail to respond to treatment.Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 andp53and the apoptotic proteins, mcl-1, bax, bcl-xl, bcl-2,Fas receptor, Fas ligand, caspase-3, M30 and PARP as potentialpredictive factors. Patients and methods:In biopsy specimens of livermetastases from 31 colorectal cancer patients, protein expression wasretrospectively determined by immunohistochemistry and related toresponse to hepatic arterial or intravenous (i.v.) 5-fluorouracil (5-FU)treatment, time to tumour progression (TTP) and overall survival. Results:Expression of both p53and Rb correlatedwith survival benefit after 5-FU treatment. A median survival time of 79weeks was found in patients with high levels of p53or Rbcompared to 36 and 44 weeks for patients expressing low levels ofp53(P = 0.027) or Rb (P = 0.030),respectively. Multivariate analysis showed that p53was thebest predictor of survival independent of sex, age or prior treatment.Following 5-FU hepatic arterial infusion, patients with a high TSexpression had a shorter survival time than those with a low expression(P = 0.025). The anti-apoptotic protein mcl-1wasthe only factor, which correlated with response to 5-FU treatment.Thirty-five percent of patients with a diffuse mcl-1expressionresponded whereas ninety percent of patients with a peri-nuclearexpression responded (P = 0.041). Conclusions:These results indicate that besides TS, alsoRb, p53and mcl-1are correlated with clinical outcomein patients with liver metastases from colorectal cancer.