Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection

Yang, Yubo; Nagano, Hiroaki; Ôta, Hideo; Morimoto, Osakuni; Nakamura, Masato; Wada, Hiroshi; Noda, Takehiro; Damdinsuren, Bazarragchaa; Marubashi, Shigeru; Miyamoto, Atsushi; Takeda, Yutaka; Dono, Keizo; Umeshita, Koji; Nakamori, Shoji; Wakasa, Kenichi; Sakon, Masato; Monden, Morito

doi:10.1016/j.surg.2006.06.033

Cited by 188 publications

(154 citation statements)

References 26 publications

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“…Although recent advances in understanding of HCC, the molecular pathogenesis of HCC remains rather elusive. Indeed, the clinical heterogeneity of HCC and lack of good treatment strategies have rendered this disease a great challenge (Yang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

Zhao¹,

Jia²,

Yang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

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Section: Introductionmentioning

confidence: 99%

S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

Zhao¹,

Jia²,

Yang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…2 The high rate of recurrence or metastases after curative resection leads to worse prognosis in HCC. 3,4 Recently, several authors have reported the positive immunoexpression of cytokeratin (CK) 19 in HCC, and CK19-positive HCC has been shown to have a high metastatic potential, which is associated with a poor prognosis. [5][6][7][8][9][10] The expression of CK19 in HCC is implicated as a novel predictor for the poor prognosis of the patients after curative resection.…”

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confidence: 99%

Epidermal growth factor induces cytokeratin 19 expression accompanied by increased growth abilities in human hepatocellular carcinoma

Yoneda

Sato

Kitao

et al. 2011

Laboratory Investigation

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Cytokeratin (CK) 19-positive hepatocellular carcinoma (HCC) has been reported to have a poor prognosis. The mechanism of the development of CK19-positive HCC remains to be studied. To clarify this, in vitro experiments were performed using human HCC cell lines HepG2), and the phenotypic changes after stimulation with several growth factors were examined using quantitative reverse transcriptase PCR, western blotting, and immunofluorescence staining. In vivo experiments using human HCC specimens obtained from a total of 78 patients and clinicopathological analysis were also performed. Among the growth factors tested, epidermal growth factor (EGF) had prominent effects on inducing CK19 expression in PLC-5 and HepG2, which was accompanied by the reduced expression of a-fetoprotein in PLC-5. The induction of CK19 expression after EGF stimulation was accompanied by the phosphorylation of c-Jun-N-terminal kinase (JNK)/stress-activated protein kinase, which was blocked by the addition of JNK inhibitors. EGF also increased proliferative abilities and invasive properties of the HCC cell lines. In vivo, 9 (12%) of 78 HCC cases showed positive immunohistochemical staining of CK19. The extent of positive immunhistochemical signals of EGF, EGF receptor (EGFR), and JNK expression was significantly intense in CK-19-positive HCC than those of CK19-negative HCC. Clinicopathological analysis showed that CK19-positive HCC had a high incidence of portal vein invasion, extrahepatic metastasis and an early relapse, which was associated with the worsened 2-year disease free survival. These results indicate that the activation of the EGF-EGFR signaling pathway is associated with the development of CK19-positive HCC, and the EGF-induced increase in growth abilities of HCC may account for the poor prognosis of the patients.

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“…Particularly in Europe and North America, the incidences of HCC have increased markedly in the last decade and will increase further in the upcoming two decades due to hepatitis C virus (HCV) infection (Deuffic et al, 1998;El Serag, 2004). Despite much effort in HCC research, the prognosis of HCC remains poor because of both a high frequency of intrahepatic recurrence (IHR; Iizuka et al, 2003Iizuka et al, , 2004Llovet et al, 2003) and high mortality of associated with extrahepatic recurrence (EHR) in distant organs (Itoh et al, 2002;Yang et al, 2007). Therefore, new non-invasive prognostic markers are urgently needed to improve the prognosis of HCC, especially of HCV-related HCC.…”

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confidence: 99%

“…It was reported that HCC recurred in distant organs in only 3 (7%) of 42 patients who underwent liver transplantation, a radical curative treatment strategies (Nart et al, 2003). A recent large study by Yang et al (2007) showed that, among 348 HCC patients who underwent hepatectomy, 47 (13.5%) had EHR during the follow-up period of 4.8 ± 3.7 years. Thus, the frequency of EHR is lower than that of early IHR; however, once HCC progresses to EHR, it is difficult to control the lesions in most cases because of the limited resectability.…”

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confidence: 99%

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

et al. 2007

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In a previous study, we showed that levels of cell-free DNA (cfDNA) were significantly higher in sera of patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) than in sera of non-HCC patients with HCV. To confirm this finding, we analysed serum cfDNA levels in a cohort of 96 patients with HCV-related HCC and in 100 HCV carriers without known HCC. Again we found that serum cfDNA levels were significantly higher in HCC patients than in HCV carriers (115.9 ± 98.3 vs 34.4 ± 40.4 ng ml À1 (mean ± s.d.), Po0.0001). Of 87 eligible patients who underwent curative hepatectomy, those with a high cfDNA level had a significantly shorter overall survival (OS) time than those in whom the cfDNA level was not high. Cox proportional hazards model showed the cfDNA level to be an independent prognostic factor for OS and cancer recurrence in distant organs. Our results suggest that the serum cfDNA level reflects the metastatic potential of HCV-related HCC and that it can be a useful predictive biomarker for distant metastasis after curative surgery.

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Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection

Cited by 188 publications

References 26 publications

S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

Epidermal growth factor induces cytokeratin 19 expression accompanied by increased growth abilities in human hepatocellular carcinoma

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

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