Natural history of inoperable hepatocellular carcinoma: Estrogen receptors' status in the tumor is the strongest prognostic factor for survival

Clinical course in hepatocellular carcinoma may be very different. We prosp ectively evaluated 96 patients with hepatocellular carcinoma unsuitable For radical therapy to investigate Factors that could influence survival. Clin ical, pathologic, and molecular data of patients were analyzed by univariat e and multivariate analysis. The overall actuarial probability of survival at year 1, 2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univar iate analysis, alphafetoprotein (AFP) (P = .0082); alkaline phosphatase (P = .0281); bilirubin (P = .0076); etiology (P = .0001); increment of turner mass at month 3 (P = .0051); type of estrogen receptor (ER) in the tumor (P = .0000); prothrombin time (P = .0003); and portal vein thrombosis (P = .0 000) had prognostic significance. At multivariate analysis, only type of ER (P = .0000) and bilirubin (P = .0030) showed independent predictive value for mortality. Survival was significantly longer in patients with wild-type estrogen receptors (P = .0000). Cumulative probability of survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for wild-type an d 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive a fter 4 years). Hepatitis B surface antigen (HBsAg)-positive patients with v ariant ERs had a median survival of 8 months versus 45 months in antihepati tis C virus-positive patients with wild-type ERs (P = .0001). In conclusion , (1) the presence of variant liver ER transcripts in the tumor was the str ongest negative predictor of survival in inoperable hepatocellular carcinom a; (2) their presence was associated with spontaneous survival significantl y worse than in patients with wild-type estrogen receptors; and (3) HBsAg-p ositive patients with variant receptors were characterized by the worst sur vival.