Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
PLoS One. 2021 Nov 3;16(11):e0259330. doi: 10.1371/journal.pone.0259330. eCollection 2021.
Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A "high" TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a "high" score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A "high" 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11-0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.
子宫内膜癌（EC）是最常见的妇科癌症。然而，目前尚无用于鉴别恶性和癌前子宫内膜病变的常规生物标志物。Ten-eleven translocation（TET）蛋白，特别是 TET1，被发现通过将 5-甲基胞嘧啶（5-mC）转化为 5-羟甲基胞嘧啶（5-hmC），在 DNA 去甲基化中发挥重要作用。TET1、5-mC 和 5-hmC 在子宫内膜癌变中的表达谱尚不清楚。我们对 181 例子宫内膜样本进行了基于医院的回顾性 TET1、5-mC 和 5-hmC 的免疫组织化学表达研究。所有正常子宫内膜（100.0%和 100.0%）和大多数非典型性子宫内膜增生（90.9%和 78.8%）和非典型性增生（90.6%和 93.8%）病例中均观察到“高”TET1 和 5-hmC 表达评分，但在不到一半的 EC 样本中发现“高”评分（分别为 48.8%和 46.5%）。TET1 和 5-hmC 表达评分在正常子宫内膜和癌前子宫内膜病变中明显高于 EC（p<0.001）。ECs（81.4%）中“高”5-mC 表达评分较正常子宫内膜（40.0%）、非典型性子宫内膜增生（51.5%）和非典型性增生（53.1%）更为常见（p<0.001）。我们还发现 TET1 mRNA 表达在 EC 中低于正常组织（p=0.0037）。TET1 免疫组化（IHC）评分与 TET1 mRNA 水平高度相关，因此我们总结 TET1 IHC 评分可用于生物标志物的确定。最重要的是，EC 病例中 TET1 评分较高与总生存率（OS）率较高相关，死亡风险比（HR）为 0.31（95%置信区间：0.11-0.84）。我们的研究结果表明，TET1、5-mC 和 5-hmC 的表达可能是鉴别恶性和癌前子宫内膜病变的潜在组织病理学生物标志物。TET1 也是 EC 的潜在预后标志物。
