Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma

Submitted: 21 December 2015
Accepted: 26 February 2016
Published: 11 April 2016
Abstract Views: 1708
PDF: 632
HTML: 408
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Hepatocellular carcinoma (HCC) represents a major global health problem, since more than 90% of primary liver cancers worldwide are HCC. Most cases of HCC are secondary to viral hepatitis infection (hepatitis B or C), alcoholism and cirrhosis. Sorafenib, an oral tyrosine kinase inhibitor that suppresses tumor proliferation and angiogenesis, emerged as the first effective systemic treatment for HCC after 30 years of research, and is currently the standard-of-care for patients with advanced HCC. Sorafenib is metabolized by cytochrome P450 (CYP450), particularly from the 3A4 isoform, producing two main metabolites: the N-oxide and the N-hydroxymethyl metabolite. We studied 11 HCC sample showing the presence of CYP3A4 and CYP3A7 in most of the samples analyzed. Specifically, the immunoreactivity of CYP3A4 was more strong and widespread than that of CYP3A7. The CYP3A4 immunoreactivity was observed in surrounding hepatocytes in 8 out of 11 cases; while the CYP3A7 immunostaining was found in normal liver cells, in 7 out of 11 cases. These results suggest the existence of a marked inter-individual variability regarding the presence of the isoforms of CYP3A. In addition, since sorafenib is metabolized by CYP3A4, but not by CYP3A7, an overexpression of CYP3A4 may lead to an increase in the degradation of the drug and then to clinical ineffectiveness. These results might implicate the necessity of an individualized approach in the treatment of HCC as positivity to CYP3A4 in HCC liver samples might predict a scarce response to sorafenib.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

How to Cite

Fanni, D., Manchia, M., Lai, F., Gerosa, C., Ambu, R., & Faa, G. (2016). Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma. European Journal of Histochemistry, 60(2). https://doi.org/10.4081/ejh.2016.2614

Similar Articles

1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.

Publication Facts

Metric
This article
Other articles
Peer reviewers 
1
2.4

Reviewer profiles  N/A

Author statements

Author statements
This article
Other articles
Data availability 
N/A
16%
External funding 
N/A
32%
Competing interests 
N/A
11%
Metric
This journal
Other journals
Articles accepted 
57%
33%
Days to publication 
111
145

Indexed in

Editor & editorial board
profiles
Academic society 
N/A