Autoren:	Ridder, Dirk Andreas Weinmann, Arndt Schindeldecker, Mario Urbansky, Lana Louisa Berndt, Kristina Gerber, Tiemo Sven Lang, Hauke Lotz, Johannes Lackner, Karl J. Roth, Wilfried Straub, Beate Katharina
Titel:	Comprehensive clinicopathologic study of alpha fetoprotein-expression in a large cohort of patients with hepatocellular carcinoma
Online-Publikationsdatum:	5-Sep-2022
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Alpha fetoprotein (AFP) is the most widely used diagnostic and prognostic serum biomarker for hepatocellular carcinoma (HCC). Despite its wide clinical use, a systematic clinicopathologic study comparing AFP expression in HCC in situ with serum AFP concentrations has not yet been conducted. To analyze AFP expression in a large cohort of patients by immunohistochemistry, we employed a comprehensive tissue microarray with 871 different HCCs of overall 561 patients. AFP immunoreactivity was detected in only about 20% of HCC core biopsies, whereas 48.9% of the patients displayed increased serum values (>12 ng/mL). Immunostaining of whole tumor slides revealed that lack of detectable immunoreactivity in core biopsies in a subgroup of patients with elevated AFP serum concentrations is due to heterogeneous intratumoral AFP expression. Serum AFP concentrations and AFP expression in situ were moderately correlated (Spearman's rank correlation coefficient .53, P = 1.2e − 13). High AFP expression detected in serum (>227.3 ng/mL) or in situ predicted unfavorable prognosis and was associated with vascular invasion, higher tumor grade and macrotrabecular-massive tumor subtype. Multivariate and ROC curve analysis demonstrated that high AFP concentrations in serum is an independent prognostic parameter and represents the more robust prognostic predictor in comparison to AFP immunostaining of core biopsies. The previously published vessels encapsulating tumor clusters (VETC) pattern turned out as an additional, statistically independent prognostic parameter. AFP-positivity was associated with increased tumor cell apoptosis, but not with increased vascular densities. Additionally, AFP-positive tumors displayed increased proliferation rates, urea cycle dysregulation and signs of genomic instability, which may constitute the basis for their increased aggressiveness.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7673
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY-NC-ND
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Zeitschrift:	International journal of cancer 150 6
Seitenzahl oder Artikelnummer:	1053 1066
Verlag:	Wiley-Liss
Verlagsort:	Bognor Regis
Erscheinungsdatum:	2022
ISSN:	1097-0215
DOI der Originalveröffentlichung:	10.1002/ijc.33898
Enthalten in den Sammlungen:	JGU-Publikationen