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

Abstract

Clinical course in hepatocellular carcinoma may be very different. We prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for radical therapy to investigate factors that could influence survival. Clinical, pathologic, and molecular data of patients were analyzed by univariate 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 univariate analysis, alphafetoprotein (AFP) (P ‫؍‬ .0082); alkaline phosphatase (P ‫؍‬ .0281); bilirubin (P ‫؍‬ .0076); etiology (P ‫؍‬ .0001); increment of tumor 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 ‫؍‬ .0000) 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 and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive after 4 years). Hepatitis B surface antigen ( Survival of patients with hepatocellular carcinoma (HCC) as reported in different series of patients is extremely variable, ranging from a few months to several years. 1-6 Different studies, especially from Japan, have shown that differences in survival may be related not only to the size of the tumor or the presence of extrahepatic metastasis 5 but also to the stage of the underlying cirrhotic disease, survival being much shorter in patients with decreased serum albumin and increased bilirubin. 1 A relevant characteristic of a subgroup of these tumors, which has been underlined but not explained by different investigators, 2,3 is a remarkable difference in growth speed, which determines significantly different doubling times 2 ; furthermore, a sudden increase in tumor growth rate has been described in some tumors, even in those that were very small at presentation. 2 A similar behavior has also been evidenced in a western epidemiologic setting in a series of untreated patients with HCC 3 : in some patients tumors had a very short doubling time (Ͻ150 days) and in others doubling time was much longer (Ͼ300 days). Using a score based on albumin, alcohol intake, number of nodules, echo pattern, and histologic type, the investigators were able to predict which patients would be characterized by long doubling time 4 ; also remarkable was the lack of significant correlation between initial size of the tumor and subsequent doubling times. 4 A practical consequence of this highly variable behavior is that, despite implementation of screening programs, not more than 20% to 40% of HCCs are detected at curable stage. 7 We have previously shown that HCC, especially in men, is characterized by an exon 5-deleted estrogen receptor transcript, which gives rise to an estrogen receptor al...

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

“…PVTT can also decrease portal flow that may lead to ascites, jaundice, hepatic encephalopathy, or liver failure. Therefore, the presence of PVTT is one of the most significant prognostic factors of poor prognosis [21,22] , and it has been reported that these patients survive only 2.7-4 mo if left untreated [22,23] . In advanced HCC patients with PVTT, standard treatments have not been established, especially in the Asia-Pacific region.…”

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

“…In contrast to a series of other published studies (Chevret et al, 1999;Llovet et al, 1999; The Cancer of the Liver Italian Program, 2000; Villa et al, 2000;Rabe et al, 2001;Herold et al, 2002), this study included a high number of patients treated by TACE and PEI, which have become the most frequently used treatments in the Western World. No patient was excluded from our retrospective analysis in contrast to those studies, who investigated only the effect of surgery or local ablative therapy (Tanaka et al, 1998;Schlitt et al, 1999;O'Suilleabhain et al, 2003;Jaeck et al, 2004).…”

HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice

“…18 HBsAg-positive patients with variant estrogen receptor ␣ (ER-␣) were characterized by the worst survival. 19 In this study, we checked the expression of androgen receptor, ER-␣, and ER-␤ in HBV gene knock-in transgenic mice by Northern blot analysis. The expression of androgen receptor and ER-␣ had not been detected in livers of the HBV transgenic mice and controls (data not shown), but the expression of ER-␤ was extremely elevated at the transcriptional level only in the liver tumors developed in male p21-HBsAg transgenic mice (Fig.…”