Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1732, USA.
Mod Pathol. 2012 Aug;25(8):1140-8. doi: 10.1038/modpathol.2012.64. Epub 2012 Mar 30.
Thyroid transcription factor-1 (TTF-1) is a DNA-binding protein that is mainly expressed in thyroid and lung tissue, but has also been found in gynecologic tissue. Recent studies have suggested that TTF-1 has tumor suppressor function in lung adenocarcinoma models. In the current study, we examined whether expression of TTF-1 in benign endometrium and endometrial hyperplasia might impact on the risk of developing endometrial cancer. Formalin-fixed paraffin-embedded endometrial tissues obtained from 535 cases were used to construct an endometrial tissue microarray. One hundred fifty of 207 patients had multiple serial endometrial specimens including 46 patients who progressed to endometrial cancer. The tissue microarray included a range of histopathologies including benign endometrium (n=231), simple hyperplasia (n=105), complex hyperplasia (n=36), simple atypical hyperplasia (n=10), complex atypical hyperplasia (n=44), and endometrial carcinoma (n=109). Expression of TTF-1 by immunohistochemistry in benign endometrium and endometrial hyperplasia was correlated with progression to cancer and clinical features known to be associated with increased risk of developing endometrial cancer. Carcinoma specimens showed a significantly greater expression of TTF-1 compared with benign endometrium and non-atypical hyperplasia (P=0.0007 and P=0.05). Presence of TTF-1 expression in benign endometrium was associated with a significantly decreased risk of cancer development (P=0.003, hazards ratio=0.104, 95% CI: 0.024-0.455). TTF-1 expression in hyperplasia did not significantly correlate with progression to cancer. The data from our study show that TTF-1 expression in normal endometrium is associated with a reduced risk of endometrial cancer development. This observation suggests that TTF-1 might function as a tumor suppressor in endometrial tissue. TTF-1 expression in normal endometrium could potentially provide clinically useful information as a biomarker for the risk of endometrial cancer.
甲状腺转录因子-1（TTF-1）是一种 DNA 结合蛋白，主要在甲状腺和肺部组织中表达，但也在妇科组织中发现。最近的研究表明，TTF-1 在肺腺癌模型中具有肿瘤抑制功能。在本研究中，我们研究了良性子宫内膜和子宫内膜增生中 TTF-1 的表达是否会影响发生子宫内膜癌的风险。使用 535 例福尔马林固定石蜡包埋的子宫内膜组织构建子宫内膜组织微阵列。207 例患者中有 150 例有多个连续的子宫内膜标本，其中 46 例进展为子宫内膜癌。组织微阵列包括一系列组织病理学改变，包括良性子宫内膜（n=231）、单纯性增生（n=105）、复杂性增生（n=36）、单纯性不典型增生（n=10）、复杂性不典型增生（n=44）和子宫内膜癌（n=109）。用免疫组化法检测良性子宫内膜和子宫内膜增生中 TTF-1 的表达，与进展为癌症以及与增加发生子宫内膜癌风险相关的临床特征相关。与良性子宫内膜和非不典型增生相比，癌标本中 TTF-1 的表达明显更高（P=0.0007 和 P=0.05）。良性子宫内膜中 TTF-1 的表达与癌症发生的风险显著降低相关（P=0.003，危险比=0.104，95%CI：0.024-0.455）。增生中 TTF-1 的表达与癌症进展无显著相关性。本研究数据表明，正常子宫内膜中 TTF-1 的表达与子宫内膜癌发展风险降低相关。这一观察结果表明，TTF-1 可能在子宫内膜组织中作为肿瘤抑制因子发挥作用。正常子宫内膜中 TTF-1 的表达可能作为子宫内膜癌风险的生物标志物提供临床有用的信息。
