Hwang Yoon Jung, Lee Hyejung, Hong Suk Kyun, Yu Su Jong, Kim Haeryoung
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Gut Liver. 2025 Mar 15;19(2):275-285. doi: 10.5009/gnl240254. Epub 2025 Jan 8.
BACKGROUND/AIMS: Fibronectin (FN) has recently been identified as being overexpressed in patients with hepatocellular carcinoma (HCC) and deemed a promising biomarker of vascular invasion. The aim of this study was to examine the patterns of FN expression in HCC cells and their clinicopathological significance, such as their association with vascular invasion and angiogenesis patterns.
Immunohistochemical analysis of FN was conducted using tissue microarrays from 258 surgically resected HCCs and matched nontumorous liver tissues. Three distinct FN expression patterns were observed: cytoplasmic, membranous, and sinusoidal. Moderate or strong expression was considered FN-positive.
Cytoplasmic or sinusoidal FN expression was significantly more common in HCC cells than in the adjacent liver tissue (p<0.001). FN expression was detected in the membranes of HCC cells and absent in nonneoplastic hepatocytes (p<0.001). Overall survival and disease-free survival in patients with HCC cells with membranous FN expression were significantly shorter than those in patients without membranous FN expression. Membranous FN expression in HCC was significantly associated with high serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) levels, infiltrative gross type, poor Edmondson-Steiner grade, major vessel invasion, microvascular invasion, macrotrabecular massive subtype, advanced T stage, and vessel-encapsulating tumor cluster pattern. Sinusoidal pattern of FN expression in HCC was significantly associated with high serum AFP and PIVKA-II levels, infiltrative gross type, large tumor size, microvascular invasion, macrotrabecular massive subtype, and vessel-encapsulating tumor cluster patterns.
Evaluating FN expression in HCC cells may be useful for identifying aggressive cases of HCC with vascular invasion via biopsy.
背景/目的：最近发现纤连蛋白（FN）在肝细胞癌（HCC）患者中过表达，并被认为是血管侵犯的一个有前景的生物标志物。本研究的目的是检测FN在HCC细胞中的表达模式及其临床病理意义，如与血管侵犯和血管生成模式的关联。
使用来自258例手术切除的HCC及配对的非肿瘤肝组织的组织芯片进行FN的免疫组化分析。观察到三种不同的FN表达模式：细胞质、膜性和窦状。中等或强表达被视为FN阳性。
HCC细胞中细胞质或窦状FN表达明显比邻近肝组织更常见（p<0.001）。在HCC细胞膜中检测到FN表达，而在非肿瘤肝细胞中未检测到（p<0.001）。具有膜性FN表达的HCC细胞患者的总生存期和无病生存期明显短于无膜性FN表达的患者。HCC中的膜性FN表达与高血清甲胎蛋白（AFP）和维生素K缺乏诱导蛋白-II（PIVKA-II）水平、浸润性大体类型、Edmondson-Steiner分级差、大血管侵犯、微血管侵犯、大小梁块状亚型、T分期晚期和血管包绕肿瘤簇模式显著相关。HCC中FN表达的窦状模式与高血清AFP和PIVKA-II水平、浸润性大体类型、肿瘤体积大、微血管侵犯、大小梁块状亚型和血管包绕肿瘤簇模式显著相关。
评估HCC细胞中的FN表达可能有助于通过活检识别具有血管侵犯的侵袭性HCC病例。
