Hepatocellular carcinomas expressing 'stemness'-related markers: clinicopathological characteristics.
Hepatocellular carcinoma (HCC) is heterogeneous in histopathology, pathogenesis and biological behavior. There is accumulating evidence that the expression of 'stemness'-related markers such as K19, EpCAM and CD133 in HCC is associated with an aggressive biological behavior and poor clinical outcome compared to conventional HCCs that do not express stemness-related markers. Compared to conventional HCCs, these tumors more frequently demonstrate infiltrative growth patterns, vascular invasion and more intratumoral fibrous stroma, and there is a spectrum of morphological and immunophenotypic features between HCCs with stemness-related marker expression, scirrhous HCCs and combined hepatocellular-cholangiocarcinoma with stem cell features. Clinically, HCCs with stemness-related marker expression are associated with increased serum α-fetoprotein levels and a poor prognosis, and are also beginning to be noticed radiologically. These tumors have also been recognized as a specific subtype in recent molecular classifications, and increasing interest in the molecular pathogenesis of HCCs with stemness-related marker expression will shed light on the development of targeted therapy for these tumors. Therefore, it is important that pathologists identify HCCs expressing stemness-related markers such as K19 during routine pathological evaluation of surgically resected or biopsied HCC tissue, as it will help to identify a high-risk subgroup of HCCs characterized by increased chemoresistance, earlier recurrence after surgical and/or locoregional treatment, increased invasiveness/metastasis and poor overall survival. We will discuss the clinicopathological characteristics of a HCC subtype expressing stemness-related markers and its future perspectives.
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Haeryoung
H
Kim
Young Nyun
YN
Park
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D011379:Prognosis; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis
D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000509:alpha-Fetoproteins