Positive glypican-3 expression in early hepatocellular carcinoma predicts recurrence after hepatectomy

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Abstract

Background

Glypican-3 (GPC3) is a new prognostic factor after curative hepatectomy in patients with hepatocellular carcinoma (HCC), and the expression of GPC3 is known to be associated with postoperative metastasis. However, the role of GPC3 in patients with early HCC remains unknown.

Methods

We retrospectively studied 55 patients with early HCC (total 99 nodules) who underwent initial hepatectomy between 1995 and 2010. Clinicopathological features and surgical outcomes were compared in relation to GPC3 expression.

Results

The GPC3-positive expression was seen in 28 of 55 patients (50.9 %) with early HCC (44 of 99 nodules). The GPC3-positive expression was significantly associated with hepatitis C virus (HCV) infection ( P = 0.0019) and with multiple early HCCs ( P < 0.0001). The 5-year disease-free survival rate was significantly lower in patients with GPC3-positive early HCC (27 %) than in patients with GPC3-negative early HCC (62 %, P = 0.0036). The GPC3 expression was a significant independent prognostic factor for disease-free survival. However, it showed no significant difference in overall survival.

Conclusions

The GPC3 expression is capable to be a new prognostic factor for disease-free survival in patients with early HCC.

Related collections

Most cited references 27

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It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. Copyright 2008 Massachusetts Medical Society.

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Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival.

YU SAWADA, Katsuhiko Uesaka, Tadatoshi Takayama … (2012)

The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC. Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-γ ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS). GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers α-fetoprotein and/or des-γ-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N = 15) than in those with low frequencies (N = 18; P = 0.033). GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination. ©2012 AACR.

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Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis.

Morris Sherman (2010)

Hepatocellular carcinoma (HCC) is increasing in incidence in many countries, and is the most common cause of death in patients with cirrhosis. With regular surveillance, small early HCC lesions can be identified. An algorithm has been developed that allows for diagnosis of these lesions. Very early HCC lesions have high cure rates with appropriate treatment. If all these factors are in place most HCCs can be cured.

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Author and article information

Contributors

I-Pei Chen: ipchen39@gmail.com

Shun-ichi Ariizumi: ariizumi@ige.twmu.ac.jp

Masayuki Nakano: masayuki-nakano@ofunachuohp.net

Masakazu Yamamoto: +81-3-33538111 , +81-3-33575553 , yamamoto@ige.twmu.ac.jp

Journal

Journal ID (nlm-ta): J Gastroenterol

Journal ID (iso-abbrev): J. Gastroenterol

Title: Journal of Gastroenterology

Publisher: Springer Japan (Tokyo )

ISSN (Print): 0944-1174

ISSN (Electronic): 1435-5922

Publication date (Electronic): 27 March 2013

Publication date PMC-release: 27 March 2013

Publication date (Print): 2014

Volume: 49

Pages: 117-125

Affiliations

[ ]Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666 Japan

[ ]Department of Pathology, Ofuna Chuo Hospital, Ofuna, Kamakura, Kanagawa Japan

Article

Publisher ID: 793

DOI: 10.1007/s00535-013-0793-2

PMC ID: 3895193

PubMed ID: 23532638

SO-VID: c164dfa9-fe75-4de3-8093-352d025754c1

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The exclusive right to any commercial use of the article is with Springer.