CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection

Abstract

This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor–node–metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan–Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19−/GPC3+ and CK19−/GPC3− three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19−/GPC3+ HCC, then CK19−/GPC3−HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients.

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

“…The findings of Feng et al. have indicated that the HCC tissue expression of both GPC3 and CK‐19 is correlated with local recurrence in HCC patients after surgical resection …”

Advances in the study of oncofetal antigen glypican-3 expression in HBV-related hepatocellular carcinoma

“…Multivariate Cox regression analysis revealed that GPC-3 is an independent risk factor for the 5-year survival (p = 0.031) and disease-free survival rates (p = 0.047). Together with tumor differentiation, the Milan criteria, and preoperative AFP, GPC-3 is a potential indicator of a poor prognosis after liver transplantation in patients with HCC and HBV-associated cirrhosis (43,44).…”

Simple Risk Score for Prediction of Early Recurrence of Hepatocellular Carcinoma within the Milan Criteria after Orthotopic Liver Transplantation

“…The correlation between the HCC subtyping based on CK19 and GPC3 combined detection and tumor biology had been identified earlier15. It was observed that patients with CK19+/GPC3+ expression carried the highest risk of microvascular invasion, regional lymph node involvement, and intrahepatic and distant metastasis, followed by patients with CK19−/GPC3+, and finally the CK19−/GPC3− phenotype.…”