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Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?

Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had...

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Autores principales: Lee, Chao-Wei, Tsai, Hsin-I, Lee, Wei-Chen, Huang, Shu-Wei, Lin, Cheng-Yu, Hsieh, Yi-Chung, Kuo, Tony, Chen, Chun-Wei, Yu, Ming-Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832124/
https://www.ncbi.nlm.nih.gov/pubmed/31635078
http://dx.doi.org/10.3390/jcm8101736
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author Lee, Chao-Wei
Tsai, Hsin-I
Lee, Wei-Chen
Huang, Shu-Wei
Lin, Cheng-Yu
Hsieh, Yi-Chung
Kuo, Tony
Chen, Chun-Wei
Yu, Ming-Chin
author_facet Lee, Chao-Wei
Tsai, Hsin-I
Lee, Wei-Chen
Huang, Shu-Wei
Lin, Cheng-Yu
Hsieh, Yi-Chung
Kuo, Tony
Chen, Chun-Wei
Yu, Ming-Chin
author_sort Lee, Chao-Wei
collection PubMed
description Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. Methods: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan–Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. Results: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. Conclusion: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.
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spelling pubmed-68321242019-11-20 Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal? Lee, Chao-Wei Tsai, Hsin-I Lee, Wei-Chen Huang, Shu-Wei Lin, Cheng-Yu Hsieh, Yi-Chung Kuo, Tony Chen, Chun-Wei Yu, Ming-Chin J Clin Med Article Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. Methods: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan–Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. Results: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. Conclusion: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings. MDPI 2019-10-19 /pmc/articles/PMC6832124/ /pubmed/31635078 http://dx.doi.org/10.3390/jcm8101736 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Chao-Wei
Tsai, Hsin-I
Lee, Wei-Chen
Huang, Shu-Wei
Lin, Cheng-Yu
Hsieh, Yi-Chung
Kuo, Tony
Chen, Chun-Wei
Yu, Ming-Chin
Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title_full Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title_fullStr Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title_full_unstemmed Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title_short Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
title_sort normal alpha-fetoprotein hepatocellular carcinoma: are they really normal?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832124/
https://www.ncbi.nlm.nih.gov/pubmed/31635078
http://dx.doi.org/10.3390/jcm8101736
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