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Clinical significance of α‐fetoprotein: involvement in proliferation, angiogenesis, and apoptosis of hepatocellular carcinoma
Author(s) -
Mitsuhashi Noboru,
Kobayashi Souichi,
Doki Tomoko,
Kimura Fumio,
Shimizu Hiroaki,
Yoshidome Hiroyuki,
Ohtsuka Masayuki,
Kato Atsushi,
Yoshitomi Hideyuki,
Nozawa Satoshi,
Furukawa Katsunori,
Takeuchi Dan,
Suda Kosuke,
Miura Seiki,
Miyazaki Masaru
Publication year - 2008
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2008.05340.x
Subject(s) - hepatocellular carcinoma , alpha fetoprotein , medicine , immunohistochemistry , angiogenesis , carcinoma , pathology , alpha (finance) , cancer research , apoptosis , biology , construct validity , biochemistry , nursing , patient satisfaction
Background and Aim: Hepatocellular carcinoma is one of the most common cancers. α‐Fetoprotein is strongly expressed in most patients with hepatocellular carcinoma, and high levels of α‐fetoprotein expression have been reported as an independent prognostic factor. However, there have been few reports on the reasons for poor prognosis. Methods: We analyzed the correlation between serum α‐fetoprotein levels and clinicopathological findings in 37 hepatocellular carcinoma patients undergoing curative surgery. α‐Fetoprotein mRNA expression in tissue samples was analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR), while protein expression was assessed by immunohistochemistry. To assess the mechanistic correlations between α‐fetoprotein and tumor progression, we further analyzed cell proliferation (Ki‐67), angiogenesis (CD34), and apoptosis (TdT‐mediated dUTP‐biotin nick end labeling [TUNEL] assay). Results: Post‐operative serum α‐fetoprotein levels were correlated with disease‐free and overall survival, and were an independent prognostic factor for survival. α‐Fetoprotein expression, as assessed by immunohistochemistry, was strong and heterogeneous in hepatocellular carcinoma. Control livers did not express α‐fetoprotein and there was weak expression of α‐fetoprotein in adjacent regions in hepatocellular carcinoma patients. The Ki‐67 labeling index in the high serum α‐fetoprotein cases was significantly higher than in α‐fetoprotein‐negative cases ( P = 0.042). The α‐fetoprotein‐positive cases also showed a significantly higher microvessel density than α‐fetoprotein‐negative cases ( P = 0.035), whereas hepatocellular carcinoma without α‐fetoprotein overexpression had a higher apoptotic index when compared to hepatocellular carcinoma with α‐fetoprotein overexpression ( P = 0.033). Conclusion: These results indicate that the poor prognosis associated with high α‐fetoprotein is due to high cell proliferation, high angiogenesis, and low apoptosis.