Prognostic Factors After Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma

Shimada, Mitsuo; Takenaka, Katsuto; Taguchi, Kenichi; Fujiwara, Yuh; Gion, Tomonobu; Kawakami, Kiyoshi; Maeda, Takashi; Shirabe, Ken; Yanaga, Katsuhiko; Sugimachi, Keizō

doi:10.1097/00000658-199801000-00012

Cited by 151 publications

(130 citation statements)

References 28 publications

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“…On the other hand, the Apo D expression values in tumor tissue specimens were significantly associated with the histological grade of the tumor, which is one of the most important prognostic factors for patients with HCC. [28][29][30] An immunohistochemical analysis also revealed a stepwise decrease in the expression at the protein level of well to moderately and poorly differentiated HCC. The prognosis of HCC patients with a low expression of Apo D was significantly worse than that in patients with a high expression.…”

Section: Discussionmentioning

confidence: 94%

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Utsunomiya

Ogawa

Yoshinaga

et al. 2005

Intl Journal of Cancer

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We previously identified apolipoprotein D (Apo D) as a novel tumor suppressor gene based on the pharmacological unmasking of epigenetic silencing. We analyzed Apo D expression using realtime reverse transcription-PCR and evaluated its expression status based on the clinicopathological parameters of 70 patients with hepatocellular carcinoma (HCC). Immunohistochemical staining was also performed. We determined the methylation status of Apo D gene promoter by methylation-specific PCR (MSP). The Apo D gene-expression in tumor tissue was significantly lower than that in nontumor tissue (p = 0.011). A low Apo D expression significantly correlated with less-differentiated HCC ( p = 0.019). Immunohistochemical studies confirmed a decreased Apo D expression in poorly differentiated tumors. The prognosis of patients with a lower Apo D gene-expression was significantly worse than that in those with a higher expression (p = 0.028). The Apo D gene-expression was an independent prognostic factor (relative risk: 2.36, p = 0.018). An MSP assay showed a low-level of methylation in well differentiated HCC and a high-level of methylation in less differentiated tumors. Apo D may be a novel tumor suppressor gene of HCC, and its expression status may be a useful biomarker for predicting the patient outcome. ' 2005 Wiley-Liss, Inc.Key words: apolipoprotein D; hepatocellular carcinoma; histological grade; prognostic factor; methylationWe recently performed a comprehensive survey of commonly inactivated tumor suppressor genes in esophageal cancer cell lines based on functional reactivation by a demethylating agent. 1 A total of 58 silenced genes were thus identified using this approach, and one of those genes was Apolipoprotein D (Apo D). In our report, we detected the promoter hypermethylation of Apo D gene using bisulfite DNA sequencing. The methylation status of Apo D correlated closely with the Apo D expression status. Moreover, the growth suppressive activity of Apo D was also demonstrated by a colony focus assay. 1 These findings thus prompted us to analyze the clinical significance of the Apo D expression status in human cancers.Apo D, belonging to the lipocalin superfamily, is a glycoprotein of about 30 kDa found in the high-density lipoprotein fraction of human plasma. 2 The functional role of Apo D remains unclear, but the observation that this protein forms complexes with lecithin-cholesterol acyltransferase suggests that Apo D may be involved in cholesterol esterification. 3 More recently, the Apo D gene-expression was reported to be induced by retinoic acid in breast cancer cell lines. The induction of the Apo D expression was accompanied by an inhibition of cell proliferation and a progression through a more differentiated phenotype. These finding suggest that the mechanisms controlling retinoic acid-induced growth arrest, cell differentiation and Apo D synthesis may be directly coordinated in human breast cancer cells. 4 Furthermore, a low expression of Apo D determined by an immunohistochemical study was significantly as...

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Section: Discussionmentioning

confidence: 94%

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Utsunomiya

Ogawa

Yoshinaga

et al. 2005

Intl Journal of Cancer

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“…Since the presence of portal vein invasion is one of the most important prognostic factors for HCC patients (Izumi et al, 1994;Shimada et al, 1998;Ikai et al, 2004), we therefore investigated a possible correlation between EZH2 mRNA values, quantitatively determined by a real-time RT -PCR, and the prognosis of HCC patients. In the present study, however, we found no significant difference in the disease-free survival rate between the high expression group and the low expression group.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma

et al. 2005

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Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group protein family, plays a crucial role in the regulation of embryonic development and has been associated with the regulation of the cell cycle. Recently, several studies have shown that EZH2 is highly expressed in aggressive tumours, including human breast cancer, prostate cancer, and lymphomas. We thus analysed EZH2 expression using real-time reverse transcription -polymerase chain reaction, and correlated its expression status with various clinicopathological parameters in 66 patients with hepatocellular carcinoma (HCC). We found high expression of EZH2 in human liver cancer cell lines. Furthermore, EZH2 gene-expression levels in tumour tissue specimens (0.3470.52) were significantly higher (Po0.0001) than those in the corresponding nontumour tissue specimens (0.0770.09). The incidence of cancer cell invasion into the portal vein was significantly higher (Po0.001) in the high EZH2 expression group (26 of the 33, 79%) than in the low expression group (13 of the 33, 39%). However, there was no significant difference in the disease-free survival rate between the two groups. The findings of this study indicate that EZH2 mRNA expression was upregulated in human HCC and may play an important role in tumour progression, especially by facilitating portal vein invasion. British Journal of Cancer (2005) Polycomb group (PcG) proteins are known to maintain the silenced state of several developmentally regulated genes and to control the transcriptional memory of a cell (Laible et al, 1997;van der Vlag et al, 1999). Dysregulation of this gene-silencing machinery may lead to cancer (Jacobs et al, 1999;Satijin and Otte, 1999). Recently, enhancer of zeste homologue 2 (EZH2), a member of the PcG protein family, has been linked to the aggressiveness of human cancers, including lymphomas ) provided biological evidence that overexpression of EZH2 promotes oncogenic transformation. In breast epithelial cells, they observed that high expression of EZH2 induced anchorage-independent growth and cell invasion, behaviours that are hallmarks of cancer. Moreover, they found that higher expression levels of EZH2 protein were strongly associated with decreased disease-free survival and decreased overall survival for patients with breast cancer. In addition, Varambally et al (2002) reported that EZH2 was overexpressed in metastatic prostate cancer and that inhibition of EZH2 blocked prostate cell growth. EZH2 expression has also been demonstrated to have prognostic significance in patients with prostate cancer (Sellers and Loda, 2002;Varambally et al, 2002;Rhodes et al, 2003;Foster et al, 2004). Therefore, the role of EZH2 in tumour development and progression has recently become a subject of increased interest (Tonini et al, 2004). To the best of our knowledge, however, the clinicopathological and prognostic significance of the EZH2 geneexpression status has not previously been examined in digestive organ cancers. The present study thus focused on examining the relationsh...

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“…The liver accounts for 30%-91% of recurrent HCC and 40% of CRC metastases after surgery [18,[29][30][31] . The presence of satellite lesions, intrahepatic microvascular invasion and poor histological differentiation are markers for recurrence and a bad prognosis [11,32] .…”

Section: Characteristics Of Recurrent Liver Cancermentioning

confidence: 99%

“…The presence of satellite lesions, intrahepatic microvascular invasion and poor histological differentiation are markers for recurrence and a bad prognosis [11,32] . There are two distinct categories of recurrences: undetected micrometastasis due to multicentric tumor or "de novo" cancer arising as a result of an underlying carcinogenic liver disease in the liver remnant [11,30,31,33] . This distinction may have significant prognostic and therapeutic implications, but it can be difficult to make a differentiation between the two types in individual patients.…”

Section: Characteristics Of Recurrent Liver Cancermentioning

confidence: 99%

Effect of liver regeneration on malignant hepatic tumors

Shi

Line

2014

WJG

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Liver regeneration after major surgery may activate occult micrometastases and facilitate tumor growth, leading to liver tumor recurrence. Molecular changes during liver regeneration can provide a microenvironment that stimulates intrahepatic tumor propagation through alterations in cellular signaling pathways, where activation and proliferation of mature hepatocytes, hepatic progenitor cells, non-parenchymal liver cells might favor both liver regeneration and tumor growth. This review highlights recent advances of tumor growth and development in the regenerating liver, possible mechanisms and clinical implications. Key words: Hepatocellular carcinoma; Colorectal cancer; Recurrence; Liver regeneration; Hepatic progenitor cell; Epithelial to mesenchymal transition Core tip: The liver has a unique capacity for regeneration after cellular damage or partial removal of tissue, and modern liver surgery relies on this property. Liver regeneration is a complex process involving a large array of growth factors, cytokines and cells to restore hepatic mass and function. Experimental and clinical data indicate that the regeneration signals facilitate the growth of both primary and secondary liver tumors and can alter their malignant potential. This is an important mechanism underlying recurrence after liver surgery. New therapeutic strategies founded on better insight into the relationship between liver regeneration and tumor biology are needed.Shi JH, Line PD. Effect of liver regeneration on malignant hepatic tumors.

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Prognostic Factors After Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma

Abstract: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Cited by 151 publications

References 28 publications

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma

Effect of liver regeneration on malignant hepatic tumors

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