Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, β-Catenin, CD133, and Ki-67

Abstract

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults. Several studies have classified HCC into molecular subtypes aiming at detecting aggressive subtypes. The aim of the present study was to investigate the role of p53, β-catenin, CD133, and Ki-67 in subclassification of HCC into different aggressive subtypes and the correlation between those markers and the clinicopathologic characteristics of HCC patients. This retrospective study was conducted on paraffin-embedded blocks of 114 HCC specimens. Tissue microarray was constructed and immunostaining for p53, β-catenin, CD133, and Ki-67 was performed and HCC score was formulated. P53 expression was associated with old age (P=0.028), large tumor size (P=0.019), poorly differentiated HCC (P=0.012), hepatitis B virus (HBV) positivity (P=0.032), and hepatitis C virus (HCV) negativity (P =0.046). β-catenin expression was associated with small sized tumors (P=0.005), HBV negativity (P=0.027), early-staged tumors (P=0.029), and prolonged recurrence-free survival (P=0.045). High percentage of CD133 expression was associated with old patients (P=0.035) and HBV positivity (P= 0.045). Ki-67 expression was associated with large tumor size (P= 0.049), vascular invasion (P= 0.05), old age (P=0.035), and previous treatment of HCV by direct acting antiviral agents (P=0.005). Cases with high HCC score showed significant association with old patients (P=0.002), previous treatment of HCV by direct acting antiviral agents (P<0.001), large tumor size (P<0.001), and poorly differentiated tumors (P= 0.009). The proposed HCC score can divide HCC patients into subtypes necessitating tailoring of treatment strategy according to this proposed score to target and optimally treat the aggressive subtypes. This score needs to be further validated on large number of patients with longer follow-up period.

Altered Protein and Gene Expression of Beclin-1 Correlates with Poor Prognosis of Hcv-Associated Hepatocellular Carcinoma in Egyptian Patients

“…Diagnosis of HCC was confirmed by multislice triphasic computed tomography (CT) scan with or without elevated alpha fetoprotein more than 200 ng/ml (Abdou et al, 2020).…”

“…Loss of Beclin-1 in mice was found to be correlated with a reduction in autophagic vacuole formation, and an unpredicted increase in human melanoma, colon, ovarian, brain cancers and HCC (Ávalos et al, 2014). It had been stated that beclin-1 is a haplo-insufficient tumor suppressor gene, which can promote cancer through impaired autophagy and increased cell proliferation (Abdou et al, 2020). Consequently, the present study was designed to determine the expression of Beclin-1 in HCV associated-HCC cases and adjacent non-neoplastic hepatic tissues, along with its correlation to demographic, clinicopathological factors, and patient's outcome regarding overall survival and recurrence.…”

“…Tissue microarrays (TMA) were constructed for tumorous and adjacent non tumorous tissue (ANT) for all studied cases (Abdou et al, 2020). Each sample tissue was represented in three different sites on the TMA block.…”