Abstract
Histological molecular classification of hepatocellular carcinoma (HCC) is clinically important for predicting the prognosis. However, a reliable serum marker has not been established. The aim of this study was to evaluate the diagnostic value of serum Wisteria Floribunda agglutinin-positive sialylated mucin 1 (WFA-sialylated MUC1), which is a novel biliary marker, as a marker of HCC with hepatic progenitor cell (HPC)/biliary features and of prognosis. A total of 144 consecutive patients who underwent complete radiofrequency ablation of primary HCC were enrolled. A serum WFA-sialylated MUC1 level of 900 μL/mL was determined as the optimal cutoff value for prediction of immunohistochemical staining for HPC/biliary features [sialylated MUC1 and cytokeratin 19 (CK19)]. Positive staining rate of sialylated MUC1 and CK19 was significantly higher in patients with WFA-sialylated MUC1 ≥900 than those with WFA-sialylated MUC1 <900. Furthermore, cumulative incidence of HCC recurrence was significantly higher in patients with WFA-sialylated MUC1 ≥900 and on multivariate analysis, serum WFA-sialylated MUC1 levels was an independent predictor of HCC recurrence. These results revealed that serum WFA-sialylated MUC1 was associated with histological feature of HCC and recurrence after curative therapy and it could be a novel marker of HPC/biliary features in HCC and of prognosis.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms in the world[1]
We found that serum WFA-sialylated MUC1 levels constitute a reliable serum marker of a subtype of HCC with hepatic progenitor cells (HPC)/biliary features
These features were associated with positive histochemical staining for Cytokeratin 19 (CK19) and sialylated MUC1 and with an increased risk of HCC recurrence after radiofrequency ablation (RFA) therapy with curative intent. These findings indicate that serum WFA-sialylated MUC1 could be used as a non-invasive biomarker of aggressiveness of HCC
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms in the world[1]. Several studies reported that some HCCs originate from hepatic progenitor cells (HPC)[6, 7] The cells in such tumors are thought to express both hepatic and biliary features and feature heterogeneous differentiation[8]. Histological molecular classification of HCC tumors is clinically relevant for predicting the prognosis This requires either surgical resection or tumor biopsy for pathological diagnosis and, to date, a reliable serum marker to reflect HPC/biliary features of HCC and replace pathological diagnosis has not been established. We hypothesized that serum WFA-sialylated MUC1 has diagnostic value to reflect the expression of biliary feature in HCC nodules and it might, be a useful predictive marker of subtypes of HCCs with HPC/biliary features, possibly obviating the need for histochemical diagnosis. The aim of this study was to evaluate whether serum WFA-sialylated MUC1 levels reflect positive staining of CK19 and sialylated MUC-1 in HCCs and to determine the association of serum WFA-sialylated MUC1 levels and the clinical course after curative therapy
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