Department of Pathology, MacKay Memorial Hospital, Taipei.
Department of Medicine, Mackay Medical College, New Taipei City.
Appl Immunohistochem Mol Morphol. 2022;30(5):383-388. doi: 10.1097/PAI.0000000000001020. Epub 2022 Mar 29.
Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma that comprises mucinous epithelial cells. The expression of hepatocyte nuclear factor 4α (HNF4α) has been previously reported as a marker for IMA, but controversy remains regarding whether HNF4α is a reliable marker for lung IMAs. In the present study, we compared HNF4α expression levels between IMA and nonmucinous adenocarcinoma (NMA) cases using 2 different HNF4α clones. We used 2 HNF4α antibody clones, H1 and H1415, to examine HNF4α expression in 36 IMA and 40 NMA cases, which comprised the control group. HNF4α immunostaining intensity (range, 0 to 3) and percentage of intensity (range, 0% to 100%) were evaluated by 3 pathologists and ImageJ software, and average H-scores were calculated for each case. Interobserver agreement was assessed using intraclass correlation coefficient. Receiver-operating characteristic curve was used to analyze sensitivity and specificity of the clones. The mean H-score was higher in the IMA group than in the NMA group for both the H1415 (141.3 vs. 9.3) and H1 (67.3 vs. 3.4) clones. The intraclass correlation coefficient for agreement among the 4 observers was good (0.806 and 0.711). The H1415 clone exhibited comparable sensitivity (83.3% vs. 83.3%) with higher specificity (97.5% vs. 92.5%) compared with the H1 clone when using cutoff values of 36.2 (H1415) and 9.5 (H1), respectively. Our analyses suggest that HNF4α should be considered as a reliable marker for primary IMA of the lung. The H1415 clone should be preferred for use in clinical practice.
浸润性黏液性腺癌（IMA）是一种罕见的腺癌变体，由黏液上皮细胞组成。先前已有报道称肝细胞核因子 4α（HNF4α）的表达是 IMA 的标志物，但关于 HNF4α 是否是肺 IMA 的可靠标志物仍存在争议。在本研究中，我们使用两种不同的 HNF4α 克隆比较了 IMA 和非黏液性腺癌（NMA）病例之间的 HNF4α 表达水平。我们使用 HNF4α 抗体克隆 H1 和 H1415 来检测 36 例 IMA 和 40 例 NMA 病例中的 HNF4α 表达，这些病例构成了对照组。通过 3 位病理学家和 ImageJ 软件评估 HNF4α 免疫染色强度（范围为 0 至 3）和强度百分比（范围为 0%至 100%），并计算每个病例的平均 H 评分。采用组内相关系数评估观察者间的一致性。采用受试者工作特征曲线分析克隆的敏感性和特异性。对于 H1415（141.3 比 9.3）和 H1（67.3 比 3.4）克隆，IMA 组的平均 H 评分均高于 NMA 组。四位观察者之间的一致性的组内相关系数较高（0.806 和 0.711）。与 H1 克隆相比，H1415 克隆的敏感性相当（83.3%比 83.3%），但特异性更高（97.5%比 92.5%），使用的截断值分别为 36.2（H1415）和 9.5（H1）。我们的分析表明，HNF4α 应被视为原发性肺 IMA 的可靠标志物。在临床实践中，应优先使用 H1415 克隆。
