Patients with small hepatocellular carcinoma (HCC) can be cured by liver transplantation (LT). However, many patients drop out during the waiting time as a result of tumor progression. We prospectively investigated the effect of transarterial chemoembolization on long-term survival of 116 patients with HCC listed for LT. Intention-to-treat analysis revealed that patients with either complete or partial response to therapy (no vital tumor or devascularization of Ն30%, respectively) as assessed by computed tomographic scan before LT had far better 1-, 2-, and 5-year survival rates (100, 93.2, and 85.7%; and 93.8, 83.6, and 66.2%, respectively) compared with those with no response or with tumor progression (82.4, 50.7, and 19.3%). Posttransplant survival analysis showed a marked survival benefit according to transarterial chemoembolization response: patients with complete or partial response had 1-, 2-, and 5-year survival rates of 89.1, 85.1, and 85.1%, and 88.6, 77.4, and 63.9%, respectively, compared with 68.6, 51.4, and 51.4% for patients whose disease did not respond to therapy. Subgroup analysis, however, showed that these benefits were only seen in patients whose disease met the Milan criteria, but not in disease exceeding the Milan criteria but fitting the expanded University of California at San Francisco criteria. These patients were also more likely to drop out as a result of tumor progression while waiting for LT (dropout rate 12.1 vs. 2.9%) and to develop recurrent HCC (21.6 vs. 7.6%). Downstaged patients did even worse, with a dropout rate of 26.7% and a 5-year survival rate of only 25%. In conclusion, the response to preoperative chemoembolization may predict long-term outcome after LT. Liver Transpl 13:272-279, 2007. © 2007 AASLD.Received May 18, 2006; accepted October 4, 2006. The last 3 decades have seen an increasing incidence of hepatocellular carcinoma (HCC) in western countries. 1 HCC is one of the most common malignant tumors worldwide, with an estimated annual incidence of about 1 million cases. [2][3][4] The main risk factor for the development of HCC is cirrhosis, regardless of cause. 5 Standard therapy for HCC depends on the size of tumor and the stage of underlying liver disease. Patients with advanced tumor disease have no chance of curative treatment, whereas those with small HCC have the option of orthotopic liver transplantation (LT). LT has been considered the only curative treatment because it has been claimed to cure the malignant disease by replacing the premalignant cirrhotic liver. Survival and recurrence rates after LT for HCC have markedly improved over the years, in particular by appropriate selection criteria. 6-11 Despite stringent criteria for patient selection, liver transplant waiting lists are getting longer, and both Europe and the United States are facing a continually worsening discrepancy between

Several studies have shown that glypican 3 (GPC3) could be a useful diagnostic marker for hepatocellular carcinoma (HCC) and for differentiating HCC from nonneoplastic and preneoplastic liver disease. To systematically investigate the epidemiology of GPC3 expression in the liver and in other organs and tissues, we used tissue microarray technology comprising 4,387 tissue samples from 139 tumor categories and 36 nonneoplastic and preneoplastic tissue types. The immunohistochemical expression of GPC3 was assessed semiquantitatively using a 10% cutoff score and was detected in 9.2% of nonneoplastic liver samples (11/119), 16% of preneoplastic nodular liver lesions (6/38), and 63.6% of HCCs (140/220), underlining the role of GPC3 in hepatocarcinogenesis. Furthermore, several other tumors revealed consistent expression of GPC3, including squamous cell carcinoma of the lung (27/50 [54%]), testicular nonseminomatous germ cell tumors (32/62 [52%]), and liposarcoma (15/29 [52%]).

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Purpose: The major obstacle in treating ovarian cancer is the rapid development of platinum resistance during therapy. Deregulation of members of the E2F family of transcription factors is crucially involved in carcinogenesis and probably in mechanisms underlying platinum resistance. We therefore investigated the relevance of the whole set of E2F family members in predicting clinical outcome and their significance in predicting platinum resistance. Experimental Design: Real-time PCR of all E2F family members was done from 77 ovarian carcinomas, defined as our training set, and 8 healthy control samples. The correlation with clinicopathologic characteristics, platinum resistance, and survival was investigated. Furthermore, the cross-talk of E2F family members was assessed for its value in predicting survival and platinum resistance. Results: The proliferation-promoting E2F1and E2F2 were associated with grade 3 tumors and residual disease >2 cm in diameter after initial surgery. Survival analyses showed low expression of E2F1or E2F2 to be significantly associated with favorable disease-free and overall survival (E2F1, P = 0.039 and 0.047, respectively; E2F2, P = 0.009 and 0.006, respectively). In contrast, high expression of inhibiting E2F4 or E2F7 predicted favorable disease-free and overall survival (E2F4, P = 0.047 and 0.042, respectively; E2F7, P = 0.048 and 0.042, respectively). A high E2F2 to E2F4 ratio was the most valuable prognostic variable for disease-free survival in multivariate analysis (hazard ratio, 6.494; P = 0.002). Tumors considered platinum resistant were associated with lower E2F4 and E2F7 expression (P = 0.012 and 0.009, respectively) compared with platinumsensitive tumors. Again, ratios of E2F1 or E2F2 to E2F7 were the most favorable variables in predicting platinum resistance. Conclusions: We here show that deregulation of both proliferation-promoting and proliferationinhibiting E2F transcription factors and their cross-talk is crucially involved in the tumor biology of ovarian cancer and influences clinical outcome. Furthermore, down-regulation of E2F7 may contribute to mechanisms underlying platinum resistance, and calculation of ratios of proliferationpromoting E2F1to E2F7 could serve as a putative predictor of platinum resistance.