Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, People's Republic of China.
Hepatol Int. 2020 Jan;14(1):96-104. doi: 10.1007/s12072-019-10006-z. Epub 2019 Dec 12.
The diagnostic and prognostic values of glypican3 (GPC3) and glutamine synthetase (GS) proteins in hepatocellular carcinoma (HCC) have been reported, but their specificity and sensitivity remain low. Here, we applied RNAscope to improve HCC early pathological and differential diagnosis by estimating GPC3 and GS mRNAs.
We performed RNAscope and immunohistochemistry (IHC) to detect GPC3 and GS biomarkers on the tissue sections of 194 cases, including high- and low-grade liver dysplastic nodules; highly, moderately, and poorly differentiated HCCs; intrahepatic cholangiocarcinomas (ICCs); metastatic HCC; and carcinomas from other organs.
The results showed that all the cases that were negative for GPC3 by RNAscope were also negative for this protein by IHC. The use of RNAscope assay improved the GPC3 and GS specificity and sensitivity by 20-30%. Hence, HCC shows early recognition and upgrades the metastatic HCC differentiation by 23% compared with IHC (p = 0.0001, 0.0064). Meanwhile, all liver cirrhosis, cholangiocytes and non-HCC samples were negative for GPC3 and GS except lymphocytes in lymphomas, and 2 (8.3%) out of the 24 ICC samples but not in the cancer cells.
RNAscope for GPC3 and GS panel was highly specific and sensitive for the pathological identification of dysplastic nodules, early stages of HCCs, and would differentiate them from HCCs and metastatic tumors compared with IHC.
已有研究报道，磷脂酰聚糖 3（GPC3）和谷氨酰胺合成酶（GS）蛋白在肝细胞癌（HCC）中的诊断和预后价值，但它们的特异性和灵敏度仍然较低。在此，我们应用 RNAscope 技术来提高 HCC 早期病理和鉴别诊断的能力，以评估 GPC3 和 GS mRNA。
我们对 194 例组织切片进行了 RNAscope 和免疫组织化学（IHC）检测，包括高低级别肝异型增生结节；高、中、低分化 HCC；肝内胆管细胞癌（ICC）；转移性 HCC；以及来自其他器官的癌。
结果显示，所有 RNAscope 检测为 GPC3 阴性的病例在 IHC 检测中也为阴性。RNAscope 检测方法提高了 GPC3 和 GS 的特异性和灵敏度 20-30%。因此，与 IHC 相比，RNAscope 检测可更早识别 HCC，并将转移性 HCC 的鉴别率提高 23%（p=0.0001，0.0064）。同时，除了淋巴瘤中的淋巴细胞，所有肝硬化、胆管细胞和非 HCC 样本均为 GPC3 和 GS 阴性，24 例 ICC 样本中有 2 例（8.3%）为阴性，但癌细胞中没有。
与 IHC 相比，RNAscope 检测 GPC3 和 GS 面板在异型增生结节、HCC 早期阶段的病理识别中具有高度特异性和灵敏度，并可将其与 HCC 和转移性肿瘤区分开来。
