Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?

Abstract

Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. Methods: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan–Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. Results: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. Conclusion: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation

“…One reason could be the relatively low sensitivity of AFP in detecting HCC patients at the early stages of the disease (BCLC stage 0, A, and B is 18%, 64%, and 18% of the enrolled patients, respectively), in addition to the FL size (<3 cm in 40.7% of the patients) and number (single FL in 64% of the HCC patients). This finding was reported in previous studies [41,42]. Thus, this research study aims to identify a miRNAs panel to serve as a non-invasive biomarker for HCC in chronic HCV patients.…”

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China

“…Cellular membrane damage and/or eruption of tumor cells are believed to involved in the pathogenesis [ 29 ]. One study mentioned that HCC patients with negative AFP tended to be older males with less HBV infection, more non-viral etiology, and less cirrhosis [ 30 ]. Table 1 and Additional file 1 : Figure S2 A indicate a trend from high to low in median AFP levels of different patient groups, consistent with this report.…”

Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP

“…Recently, the role of serum AFP as a surveillance tool or diagnostic marker for HCC has been reduced due to its limited sensitivity and specificity. AFP is often elevated in non-cancerous conditions, such as severe inflammation, and is not elevated in as many as 40% of HCC patients [1,2,16,17]. Other proteins, such as PIVKA II or AFP L3, may aid in diagnosis [3,4], but in many cases of HCC, the expression of these biomarkers is only elevated in later stages.…”