目的:关于肝细胞癌(HCC)中肠道标志物表达的数据有限。我们确定了细胞角蛋白(CK)19的临床病理关联,这是一种祖细胞肝上皮细胞标记以及胆管上皮标记,和肠道免疫组织化学标记物在HCC中的表达,并评估其预后价值。
结果:使用CK19、CK20、CDH17、CDX2和SATB2抗体对来自202个已知HCC的组织切片和/或组织微阵列(TMA)进行免疫染色。对苏木精和伊红(H&E)染色的载玻片进行了肿瘤分级。检索临床和肿瘤结果。评估染色与临床病理特征和生存结果的关联。CK19、CK20、CDH17、CDX2和SATB2分别为12.8、5.4、10.3、8.6和59.9%,分别。除SATB2外,所有SATB2均与较高的肿瘤分级和AFP水平>400ng/ml密切相关(P<0.05)。CK19阳性HCC更可能表达CDX2(P=0.001),CDH17(P<0.001)和/或CK20(P=0.012)。CK20、CDX2和CDH17共表达5例(2.5%)。CK19和SATB2阳性,肿瘤大小≥5cm,背景肝硬化,通过对数秩检验和单变量比例风险回归,AFP>400ng/ml和没有治疗与总生存率降低相关。然而,在多变量模型中,CK19和SATB2阳性不是降低生存率的独立预测因子,而它们与已知的HCC不良预后因子的关联是明显的。
结论:肝癌可以表达肠分化标志物。这种表型异常与可变的临床病理参数相关,其中一些是生存不佳的独立预测因素。
OBJECTIVE: Data regarding expression of intestinal markers in hepatocellular carcinoma (HCC) are limited. We determined the clinicopathological associations of cytokeratin (CK)19, a progenitor liver epithelial cell marker as well as biliary epithelial marker, and intestinal immunohistochemical markers expression in HCC and assessed their prognostic value.
RESULTS: Tissue sections and/or tissue microarrays (TMAs) from 202 known HCCs were immunostained using CK19, CK20, CDH17, CDX2 and
SATB2 antibodies. Haematoxylin and eosin (H&E)-stained slides were reviewed for tumour grading. Clinical and oncological outcomes were retrieved. Associations of staining with clinicopathological features and survival outcomes were evaluated. CK19, CK20, CDH17, CDX2 and
SATB2 were positive in 12.8, 5.4, 10.3, 8.6 and 59.9%, respectively. All but
SATB2 were strongly associated with higher tumour grade and AFP levels > 400 ng/ml (P < 0.05). CK19-positive HCC were more likely to express CDX2 (P = 0.001), CDH17 (P < 0.001) and/or CK20 (P = 0.012). CK20, CDX2 and CDH17 co-expression was seen in five cases (2.5%). CK19 and
SATB2 positivity, tumour size ≥ 5 cm, background cirrhosis, AFP > 400 ng/ml and having no treatment were associated with decreased overall survival by log-rank test and univariable proportional hazards regression. However, in a multivariable model, CK19 and
SATB2 positivity were not independent predictors of decreased survival while their association with known poor prognosticators in HCC was evident.
CONCLUSIONS: HCC can express markers of intestinal differentiation. This phenotypical aberrancy correlates with variable clinicopathological parameters, some of which are independent predictors of poor survival.