Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
BMC Cancer. 2013 Mar 27;13:161. doi: 10.1186/1471-2407-13-161.
Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists.
The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients.
ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence.
ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
高级别异型增生结节（HGDN）和高分化肝细胞癌（WDHCC）的鉴别诊断对有经验的肝脏临床医生、放射科医生和肝脏病理学家来说是一个挑战。
采用免疫组织化学法检测低级别异型增生结节（LGDN）、HGDN 和 WDHCC 中氨基己糖酶-1（ACY1）、自噬相关蛋白 1（SQSTM1）和磷脂酰基醇蛋白 3（GPC3）的表达谱。通过逻辑回归模型（HGDN=21；WDHCC=32）和在独立测试集中验证（HGDN，n=21；WDHCC，n=24），研究了这三种标志物单独和联合对 HGDN 和 WDHCC 的鉴别诊断性能。在一个独立的 500 例患者组中，通过单变量和多变量分析评估术后总生存和复发时间。
ACY1、SQSTM1 和 GPC3 在各组中均有差异表达。对于 WDHCC 与 HGDN 的鉴别诊断，ACY1+SQSTM1+GPC3 联合检测 WDHCC 的敏感性和特异性在训练集中分别为 93.8%和 95.2%，高于任何两种标志物组合。四种诊断模型的有效性在独立测试集中进一步得到证实，观察到了相应的良好敏感性和特异性。有趣的是，HCC 组织中 GPC3 的表达结合血清甲胎蛋白（AFP）被发现是总生存和复发时间的独立预测因子。
ACY1+SQSTM1+GPC3 联合使用免疫组织化学法是鉴别 WDHCC 和 HGDN 的一种有潜在价值的生物标志物。同时，低 GPC3 染色结合阳性血清 AFP 可能在预测术后不良结局和高肿瘤复发风险方面具有实际作用。
