Clinical significance of alpha-fetoprotein: involvement in proliferation, angiogenesis, and apoptosis of hepatocellular carcinoma.

Abstract

BACKGROUND AND AIM:

Hepatocellular carcinoma is one of the most common cancers. alpha-Fetoprotein is strongly expressed in most patients with hepatocellular carcinoma, and high levels of alpha-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 alpha-fetoprotein levels and clinicopathological findings in 37 hepatocellular carcinoma patients undergoing curative surgery. alpha-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 alpha-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 alpha-fetoprotein levels were correlated with disease-free and overall survival, and were an independent prognostic factor for survival. alpha-Fetoprotein expression, as assessed by immunohistochemistry, was strong and heterogeneous in hepatocellular carcinoma. Control livers did not express alpha-fetoprotein and there was weak expression of alpha-fetoprotein in adjacent regions in hepatocellular carcinoma patients. The Ki-67 labeling index in the high serum alpha-fetoprotein cases was significantly higher than in alpha-fetoprotein-negative cases (P = 0.042). The alpha-fetoprotein-positive cases also showed a significantly higher microvessel density than alpha-fetoprotein-negative cases (P = 0.035), whereas hepatocellular carcinoma without alpha-fetoprotein overexpression had a higher apoptotic index when compared to hepatocellular carcinoma with alpha-fetoprotein overexpression (P = 0.033).

CONCLUSION:

These results indicate that the poor prognosis associated with high alpha-fetoprotein is due to high cell proliferation, high angiogenesis, and low apoptosis.

• Authors: Noboru Mitsuhashi, Souichi Kobayashi, Tomoko Doki, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, Masayuki Ohtsuka, Atsushi Kato, Hideyuki Yoshitomi, Satoshi Nozawa, Katsunori Furukawa, Dan Takeuchi, Kosuke Suda, Seiki Miura, Masaru Miyazaki
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 23 Issue 7 Pt 2 Pg. e189-97 (Jul 2008) ISSN: 1440-1746 [Electronic] Australia
• PMID: 18466288 (Publication Type: Journal Article)

Chemical References

• AFP protein, human
• RNA, Messenger
• alpha-Fetoproteins

Topics

• Aged
• Apoptosis
• Carcinoma, Hepatocellular (blood supply, chemistry, pathology, surgery)
• Cell Proliferation
• Disease Progression
• Disease-Free Survival
• Female
• Hepatectomy
• Humans
• Liver Neoplasms (blood supply, chemistry, pathology, surgery)
• Male
• Middle Aged
• Neovascularization, Pathologic (metabolism, pathology, surgery)
• RNA, Messenger (analysis)
• Time Factors
• Treatment Outcome
• Up-Regulation
• alpha-Fetoproteins (analysis, genetics)