Evaluating clinical and prognostic implications of Glypican-3 in hepatocellular carcinoma.

Ahmed Omar Kaseb,Ahmed Shalaby,Bharathi Vennapusa,James Yao,Janine Feng,Robert A Wolff,Reham Abdel-Wahab,Manal Hassan,Hesham M Amin,Asif Rashid,Sahin Lacin,Toshihiko Ohtomo

doi:10.18632/oncotarget.12066

Abstract

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. In patients with HCC, histopathogical differentiation is an important indicator of prognosis; however, because determination of HCC differentiation is difficult, the recently described immunohistochemical (IHC) marker glypican3 (GPC3) might assist in HCC prognostication.The goal of our study was to investigate GPC3's IHC staining pattern and define the relationship between its expression and patients' clinicopathologic features and overall survival. We retrieved clinical parameters from 101 pathologically diagnosed HCC patients' medical records and classified these patients into 4 clinical score categories (0–3) based on increasing GPC3 staining intensity and the percentage of stained tumor cells in their resection and biopsy specimens. Histopathological samples were well, moderately, and poorly differentiated in 33, 22, and 12 patients, respectively, and the GPC3 expression rate was 63%, 86%, and 92%,respectively. The median overall survival was 49.9 months (confidence interval (CI): 35.3–64.6 months) for clinical scores 0–1 and 30.7 months (CI: 19.4–41.9 months) for clinical scores 2–3. This difference was not statistically significant (P = .06) but showed a strong trend. In conclusion, a greater GPC3 expression is associated with a worse HCC prognosis and may be a promising prognostic marker.

Highlights

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and it is the fifth most common cancer in men (554,000 cases/year, 7.5% of total cancer cases) and the ninth in women (228,000 cases/year, 3.4% of total cancer cases)
Our current study indicates that higher GPC3 expression level in HCC is a risk factor for shorter overall survival (OS)
GPC3 expression may be associated with histopathologic differentiation grade and advanced clinicopathologic features, but these findings were not significant

Summary

Introduction

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and it is the fifth most common cancer in men (554,000 cases/year, 7.5% of total cancer cases) and the ninth in women (228,000 cases/year, 3.4% of total cancer cases). 745,000 people worldwide die of the disease [1]. Cirrhosis is the greatest single risk factor for HCC, and other risk factors include chronic hepatitis B or C infection, exposure to aflatoxin, alcohol abuse, fatty liver disease, and smoking. Patient prognosis is mainly dependent upon the size and number of tumor nodules, the presence or absence of portal venous invasion, and histopathological differentiation. In some cases, the distinction of tumor differentiation is challenging based on histologic grounds alone. Immunohistochemical (IHC) markers have been studied for prognostication in HCC

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