Kim Haeryoung, Park Young Nyun
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Dig Dis. 2014;32(6):778-85. doi: 10.1159/000368021. Epub 2014 Oct 29.
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.
肝细胞癌（HCC）在组织病理学、发病机制和生物学行为方面具有异质性。越来越多的证据表明，与不表达“干性”相关标志物的传统HCC相比，HCC中K19、EpCAM和CD133等“干性”相关标志物的表达与侵袭性生物学行为及不良临床预后相关。与传统HCC相比，这些肿瘤更常表现为浸润性生长模式、血管侵犯和更多的肿瘤内纤维间质，并且在具有“干性”相关标志物表达的HCC、硬化型HCC和具有干细胞特征的肝细胞胆管癌之间存在一系列形态学和免疫表型特征。临床上，具有“干性”相关标志物表达的HCC与血清甲胎蛋白水平升高及预后不良相关，并且在放射学上也开始受到关注。这些肿瘤在最近的分子分类中也被确认为一种特定亚型，对具有“干性”相关标志物表达的HCC分子发病机制的兴趣增加将有助于揭示这些肿瘤的靶向治疗发展。因此，病理学家在对手术切除或活检的HCC组织进行常规病理评估时识别出表达如K19等“干性”相关标志物的HCC非常重要，因为这将有助于识别出以化疗耐药性增加、手术和/或局部区域治疗后早期复发、侵袭性/转移性增加及总体生存率差为特征的HCC高危亚组。我们将讨论表达“干性”相关标志物的HCC亚型的临床病理特征及其未来前景。
