Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior
Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior
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表达胆管细胞表型的肝细胞癌是一种具有高度攻击行为的新亚型
DOI：
10.1245/s10434-011-1585-7
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发表时间：
2011-08-01
影响因子：
3.7
通讯作者：
Cong, Wen-Ming
中科院分区：
文献类型：
--
作者：
Lu, Xin-Yuan;Xi, Tao;Cong, Wen-Ming
背景表达胆管细胞标志物的经典型肝细胞癌（HCC）患者（我们称之为双表型HCC（DPHCC））的病理生物学特征和手术结局尚不清楚。本研究的目的是评估DPHCC.MethodsA回顾性单中心研究的DPHCC 1530例连续手术标本的病理特征的表型和病理特征之间的关联。免疫组化染色进行肝细胞（Hep Par 1/pCEA）和胆管细胞（细胞角蛋白19 [CK 19]/粘蛋白核心蛋白-1 [MUC-1]）。136例患者血清甲胎蛋白（AFP）和32例患者血清CA 19 -9升高，分别占87.7%和20.7%，且AFP升高与CK 19免疫组化染色密切相关（P< 0.01）。CK 19和MUC-1的联合表达强度与肿瘤大小、微血管浸润和卫星结节形成显著相关（P< 0.05-0.01）。与单纯HCC患者相比，DPHCC患者的总生存期（30.4 ± 3.7个月）和无复发生存期（13.2 ± 2.0个月）分别为43.6 ± 3.9个月和23.4 ± 2.5个月，P<0.05和0.01。多变量考克斯回归分析确定CK 19阳性表达是一个独立的预后因素为总生存率和复发生存率。由于DPHCC与常规HCC的形态学特征存在重叠，我们建议在HCC的病理诊断中常规使用CK 19筛查DPHCC。
BackgroundThe pathobiological features and surgical outcomes of patients with classical hepatocellular carcinoma (HCC)-expressing cholangiocyte markers that we named dual-phenotype HCC (DPHCC) remain unclear. The purpose of this study was to assess the association between the phenotype and surgicopathologic features of DPHCC.MethodsA retrospective single-center study was performed on the surgicopathologic features of DPHCC from 1530 consecutive surgical specimens. Immunohistochemical staining was performed with antibodies to hepatocytes (Hep Par 1/pCEA) and cholangiocytes (cytokeratin 19 [CK19]/mucin core protein-1 [MUC-1]).ResultsDPHCC accounted for 10.1% (n= 155) of total HCCs. The serum alfa-fetoprotein and CA19-9 were elevated in 87.7% (n= 136) and 20.7% (n= 32) of patients, respectively; the former had close correlation with the immunostaining of CK19 (P< 0.01). The combination of immunostaining intensities of CK19 and MUC-1 was significantly associated with tumor size, microvascular invasion, and satellite nodule formation (P< 0.05–0.01). Compared to patients with pure HCC, those with DPHCC had significantly lower overall survival (30.4 ± 3.7 vs. 43.6 ± 3.9 months,P< 0.05) and recurrence-free survival (13.2 ± 2.0 vs. 23.4 ± 2.5 months,P< 0.01), respectively. Multivariate Cox regression analyses identified CK19-positive expression to be an independent prognostic factor for both overall survival and recurrence-free survival.ConclusionsDPHCC is a novel surgicopathologic entity that has a highly aggressive behavior and worse postoperative prognosis than pure HCC. Because the morphological features between DPHCC and conventional HCC overlap, we recommend that CK19 be routinely used in the pathological diagnosis of HCC for screening DPHCC.