Clinico-Radio-Pathological and Molecular Features of Hepatocellular Carcinomas with Keratin 19 Expression

Hepatocellular carcinoma (HCC) is a heterogeneous neoplasm, both from the molecular and histomorphological aspects. One example of heterogeneity is the expression of keratin 19 (K19) in a subset (4 –28%) of HCCs. The presence of K19 expression in HCCs has important clinical implications, as K19-positive HCCs have been associated with aggressive tumor biology and poor prognosis. Histomorphologically, K19-positive HCCs demonstrate a more infiltrative appearance, poor histological differentiati on, more frequent vascular invasion, and more intratumoral fibrous stroma than K19-negative conventional HCCs. From the molecular aspect, K19-positive HCCs have been matched with various gene signatures that have been associated with stemness and poor prognosis, including the G1–3 groups, S2 class , cluster A, proliferation signature, and vascular invasion signature. K19-positive HCCs also show upregulated signatures related to transforming growth factor-β pathway and epithelial-to-mesenchymal transition. The main regulators of K19 expression include hepatocyte growth factor-MET paracrine si gnaling by cancer-associated fibroblast, epidermal growth factor-epidermal growth factor receptor signaling, laminin, and DNA methylation. Clinically, higher serum alpha-fetoprotein levels, frequent association with chronic hepatitis B, more invasive growth, and lymph node metastasis have been shown to be characteristics of K19-positive HCCs. Radiologic features including atypical enhancement pat...
Source: Liver Cancer - Category: Cancer & Oncology Source Type: research