Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT.
Appl Immunohistochem Mol Morphol. 2021 Mar 1;29(3):180-187. doi: 10.1097/PAI.0000000000000885.
Albumin messenger RNA (mRNA) in situ hybridization is a sensitive and specific biomarker for hepatocellular carcinoma (HCC). Intrahepatic cholangiocarcinoma (ICC) shows variable sensitivity, whereas extrahepatic cholangiocarcinoma (ECC) and metastatic carcinoma are generally negative. We studied the clinical utility and limitations of albumin mRNA detection in a cohort of HCCs, ICCs, ECCs, bile duct adenomas, bile duct hamartomas, and metastatic carcinomas to the liver; and investigated the variability in sensitivity observed for this biomarker in ICCs. We identified 122 cases of hepatobiliary lesions and metastatic carcinomas. Albumin mRNA detection was performed using RNAscope run on formalin-fixed, paraffin-embedded tissue sections. ICCs were categorized according to the classification proposed by Hayashi and colleagues into the small duct, large duct, and indeterminate subtypes. Albumin mRNA was detected in all 17 HCCs and focally in 6/8 (75%) of bile duct adenomas. All 28 nonhepatic carcinomas, 13 bile duct hamartomas, and 9 ECCs were negative. Albumin mRNA was found in 38/47 (80.9%) of ICC with 35/37 (94.6%) in the small duct subtype, 2/3 (66.7%) in the indeterminate subtype, and 1/7 (14.3%) of the large duct subtype (P<0.003). Albumin mRNA detection is a sensitive and specific biomarker for HCCs. It is highly sensitive and moderately specific in the diagnosis of ICC with small gland morphology, but not ICCs with large duct morphology and in metastatic carcinoma. The variability in the sensitivity of albumin mRNA expression in ICCs may depend on the subtypes of ICC.
白蛋白信使 RNA（mRNA）原位杂交是肝细胞癌（HCC）的一种敏感和特异的生物标志物。肝内胆管癌（ICC）显示出可变的敏感性，而肝外胆管癌（ECC）和转移性癌通常为阴性。我们研究了白蛋白 mRNA 检测在 HCC、ICC、ECC、胆管腺瘤、胆管错构瘤和转移性肝癌肝转移瘤中的临床应用及其局限性，并研究了 ICC 中观察到的这种生物标志物敏感性的变异性。我们确定了 122 例肝胆病变和转移性癌病例。使用在福尔马林固定、石蜡包埋的组织切片上运行的 RNAscope 进行白蛋白 mRNA 检测。ICC 根据 Hayashi 及其同事提出的分类分为小胆管、大胆管和不确定亚型。17 例 HCC 中均检测到白蛋白 mRNA，8 例胆管腺瘤中有 6 例（75%）呈局灶性。28 例非肝脏癌、13 例胆管错构瘤和 9 例 ECC 均为阴性。47 例 ICC 中有 38 例（80.9%）检测到白蛋白 mRNA，其中小胆管亚型 35 例（94.6%），不确定亚型 2 例（66.7%），大胆管亚型 1 例（14.3%）（P<0.003）。白蛋白 mRNA 检测是 HCC 的一种敏感和特异的生物标志物。它在小腺体形态的 ICC 的诊断中具有高度敏感性和中等特异性，但在大导管形态的 ICC 和转移性癌中则不具有特异性。ICC 中白蛋白 mRNA 表达敏感性的变异性可能取决于 ICC 的亚型。
