Naka Tomoaki, Hatanaka Yutaka, Tabata Yukiko, Takasawa Akira, Akiyama Hideo, Hida Yasuhiro, Okada Hiromi, Hatanaka Kanako C, Mitsuhashi Tomoko, Kushitani Kei, Amatya Vishwa Jeet, Takeshima Yukio, Inai Kouki, Kaga Kichizo, Matsuno Yoshihiro
Department of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, Japan.
Department of Diagnostic Pathology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
Diagnostics (Basel). 2022 Jan 27;12(2):316. doi: 10.3390/diagnostics12020316.
Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: and . Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers.
尽管免疫组织化学的常规应用提高了临床实践中组织病理学诊断的准确性，但仍需要发现新型诊断标志物的新方法。我们采用反向转化方法，利用来自一例极为罕见病例的有限存档组织，寻找恶性胸膜间皮瘤（MPM）的新型诊断标志物。从由MPM和肺腺癌（PAC）组成的同步碰撞肿瘤的福尔马林固定石蜡包埋（FFPE）组织中提取的总RNA用于基因表达谱（GEP）分析。在GEP分析选择的54个基因中，我们最终鉴定出以下两个MPM候选标志物基因： 和 。对48例MPM和20例PAC病例的免疫组织化学分析表明，磷酸甘油酸脱氢酶（PHGDH）和三聚体基序蛋白29（TRIM29）的敏感性和特异性几乎与钙视网膜蛋白相当（敏感性分别为50%、46%和63%，特异性分别为95%、100%和100%）。重要的是，在23例上皮样MPM中，所有3例钙视网膜蛋白阴性病例的TRIM29均为阳性。这两种标志物在MPM和PAC的免疫组织化学鉴别诊断中可能具有实用价值。这种基于一例极罕见病例的FFPE样本的成功反向转化方法，鼓励进一步利用此类样本开发新型诊断标志物。
