Department of Medical Genetics, The University of British Columbia, Vancouver, BC, V6H 3N1, Canada; Molecular Oncology, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
Molecular Oncology, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
Hum Pathol. 2021 Feb;108:1-11. doi: 10.1016/j.humpath.2020.10.005. Epub 2020 Oct 26.
Mesonephric carcinomas (MEs) and female adnexal tumors of probable Wolffian origin (FATWO) are derived from embryologic remnants of Wolffian/mesonephric ducts. Mesonephric-like carcinomas (MLCs) show identical morphology to ME of the cervix but occur in the uterus and ovary without convincing mesonephric remnants. ME, MLC, and FATWO are challenging to diagnose due to their morphologic similarities to Müllerian/paramesonephric tumors, contributing to a lack of evidence-based and tumor-specific treatments. We performed whole-proteomic analysis on 9 ME/MLC and 56 endometrial carcinomas (ECs) to identify potential diagnostic biomarkers. Although there were no convincing differences between ME and MLC, 543 proteins showed increased expression in ME/MLC relative to EC. From these proteins, euchromatic histone lysine methyltransferase 2 (EHMT2), glutathione S-transferase Mu 3 (GSTM3), eukaryotic translation elongation factor 1 alpha 2 (EEF1A2), and glycogen synthase kinase 3 beta were identified as putative biomarkers. Immunohistochemistry was performed on these candidates and GATA3 in 14 ME/MLC, 8 FATWO, 155 EC, and normal tissues. Of the candidates, only GATA3 and EHMT2 were highly expressed in mesonephric remnants and mesonephric-derived male tissues. GATA3 had the highest sensitivity and specificity for ME/MLC versus EC (93% and 99%) but was absent in FATWO. EHMT2 was 100% sensitive for ME/MLC & FATWO but was not specific (65%). Similarly, EEF1A2 was reasonably sensitive to ME/MLC (92%) and FATWO (88%) but was the least specific (38%). GSTM3 performed intermediately (sensitivity for ME/MLC and FATWO: 83% and 38%, respectively; specificity 67%). Although GATA3 remained the best diagnostic biomarker for ME/MLC, we have identified EHMT2, EEF1A2, and GSTM3 as proteins of interest in these cancers. FATWO's cell of origin is uncertain and remains an area for future research.
中肾管癌（MEs）和可能来源于 Wolffian 起源的女性附属肿瘤（FATWO）来源于 Wolffian/中肾管的胚胎残余。中肾样癌（MLCs）与宫颈 ME 的形态相同，但发生在子宫和卵巢中，没有令人信服的中肾残余。由于其形态与 Müllerian/副中肾管肿瘤相似，ME、MLC 和 FATWO 的诊断具有挑战性，导致缺乏基于证据和肿瘤特异性的治疗方法。我们对 9 例 ME/MLC 和 56 例子宫内膜癌（ECs）进行了全蛋白质组分析，以确定潜在的诊断生物标志物。尽管 ME 和 MLC 之间没有明显差异，但 543 种蛋白质在 ME/MLC 中的表达相对于 EC 增加。从这些蛋白质中，鉴定出 euchromatic histone lysine methyltransferase 2（EHMT2）、glutathione S-transferase Mu 3（GSTM3）、eukaryotic translation elongation factor 1 alpha 2（EEF1A2）和 glycogen synthase kinase 3 beta 作为潜在的生物标志物。在 14 例 ME/MLC、8 例 FATWO、155 例 EC 和正常组织中对这些候选物和 GATA3 进行了免疫组织化学染色。在中肾残余和中肾源性男性组织中，只有 GATA3 和 EHMT2 高度表达。GATA3 在 ME/MLC 与 EC 相比具有最高的敏感性和特异性（93%和 99%），但在 FATWO 中不存在。EHMT2 对 ME/MLC 和 FATWO 的敏感性为 100%，但特异性为 65%。同样，EEF1A2 对 ME/MLC 和 FATWO 的敏感性相当（92%和 88%），但特异性最低（38%）。GSTM3 的性能居中（ME/MLC 和 FATWO 的敏感性分别为 83%和 38%，特异性为 67%）。尽管 GATA3 仍然是 ME/MLC 的最佳诊断生物标志物，但我们已经确定 EHMT2、EEF1A2 和 GSTM3 是这些癌症中感兴趣的蛋白质。FATWO 的细胞起源尚不确定，仍是未来研究的一个领域。
