Original Contribution
The American Journal of Gastroenterology (2006) 101, 524–532; doi:10.1111/j.1572-0241.2006.00443.x
Diagnostic and Prognostic Role of 
-Fetoprotein in Hepatocellular Carcinoma: Both or Neither?
Supported in part by a grant by MURST.1
Fabio Farinati MD1, Dario Marino MD1, Massimo De Giorgio MD1, Anna Baldan MD1, Maria Cantarini MD1, Carmela Cursaro MD1, Gianludovico Rapaccini MD1, Paolo Del Poggio MD1, Maria Anna Di Nolfo MD1, Luisa Benvegnù MD1, Marco Zoli MD1, Franco Borzio MD1, Mauro Bernardi MD1 and Franco Trevisani MD1 Italian Liver Cancer (ITALICA) group
1Other members of the ITALICA group: Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Semeiotica Medica, Alma Mater Studiorum, Università di Bologna: Pietro Andreone, Chiara Bendini, Maurizio Biselli, Paolo Caraceni, Marco Domenicali, Annagiulia Gramenzi, Silvia Li Bassi, Donatella Magalotti, Giulia Magini, Federica Mirici Cappa, Valentina Santi, Andrea Zambruni; Dipartimento di Medicina Interna e Gastroenterologia Alma Mater Studiorum, University of Bologna: Antonio Maria Morselli-Labate; Cattedra di Medicina Interna II, Università Cattolica del Sacro Cuore di Roma: Marco Covino, Giovanni Gasbarrini; Cattedra di Malattie dell'Apparato Digerente, Università di Padova; Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica V, Università di Padova: Alfredo Alberti, Angelo Gatta, Maurizio Gios; Dipartimento di Discipline Chirurgiche, Rianimatorie e dei Trapianti, Università di Bologna: Gian Luca Grazi, Bruno Nardo, Matteo Ravaioli; Divisione di Medicina, Ospedale Treviglio-Caravaggio, Treviglio: Lodovico Gilardoni, Mario Mattiello; Divisione di Medicina, Ospedale Bolognini, Seriate: Maria Di Marco, Elena Vavassori; Dipartimento di Scienze Radiologiche ed Istocitopatologiche, Università di Bologna: Cristina Rossi
Correspondence: Fabio Farinati, Department of Surgical and Gastroenterological Sciences, Universitary Policlinic, Via Giustiniani 2, 35128 Padova, Italy
Received 24 May 2005; Revised 0000; Accepted 26 October 2005.
Abstract
BACKGROUND:
The clinical usefulness of 
-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.
OBJECTIVES:
To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype.
METHODS:
A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor–nodes–metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.
RESULTS:
Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21–400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1–4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001).
CONCLUSION:
The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.
