From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures
From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures
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DOI：
10.1097/cej.0b013e32811080ce
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发表时间：
2008-04-01
影响因子：
2.4
通讯作者：
Blankstein, Josef
中科院分区：
文献类型：
--
作者：
Boruban, Melih C.;Altundag, Kadri;Blankstein, Josef
子宫内膜增生与高分化癌的组织学鉴别诊断仍存在争议。用现有的标志物预测子宫内膜增生伴子宫内膜癌患者的子宫内膜癌尚不可靠。因此，这些患者在临床管理中需要更多的关注。子宫内膜增生是指子宫内膜腺体增生，导致腺体与间质比例升高。细胞学异常可能发展为子宫内膜癌或与之共存，是由于雌激素的刺激而不受孕激素的抑制。在子宫内膜增生或癌症的情况下，其表达改变的生物标志物，如孕酮受体、胰岛素样生长因子1、视黄醇脱氢酶11型和分泌型卷曲相关蛋白4，似乎有希望用作早期肿瘤标志物。83%的子宫内膜腺癌病例中存在PTEN突变，使其成为1型子宫内膜肿瘤中最常见的早期分子遗传学改变，通常与增生相关。p53基因突变在子宫内膜增生中未发现，但研究人员在20%的子宫内膜癌病例和90%的浆液性子宫内膜肿瘤病例中检测到该突变。环氧合酶-2在增生的肿瘤转化中起重要作用。环氧合酶-2的表达减少细胞凋亡，增加血管生成，并与侵袭性有关。高分化子宫内膜腺癌中环氧合酶-2表达显著增加。已知前列腺素E-2调节芳香化酶基因表达，并且是环氧合酶-2的产物。芳香化酶抑制剂的数据是有希望的，在乳腺癌患者中，他莫昔芬治疗诱导子宫异常早在治疗开始后3个月。相反，这些异常在接受芳香化酶抑制剂的患者中未见，并且在他莫昔芬停药后转换治疗可能逆转他莫昔芬相关的子宫内膜增厚。
Controversies are still seen in the histological differential diagnosis of hyperplasia and well-differentiated endometrial carcinoma. Prediction of endometrial cancer in patients with hyperplasia with atypia, with the available markers has not been reliable yet. Hence these patients require more attention in the clinical management. Endometrial hyperplasia is proliferation of endometrial glands resulting in a higher gland: stroma ratio. Cytological atypia, which may progress to or co-exist with endometrial cancer and other pathological changes, result from estrogen stimulation unopposed by progesterone. Biomarkers whose expression is altered in cases of endometrial hyperplasia or cancer such as progesterone receptor, insulin-like growth factor 1, retinaldehyde dehydrogenase type 11, and secreted frizzled-related protein 4, seem to be promising to use as early-stage tumor markers. Mutation of PTEN is present in 83% of endometrial adenocarcinoma cases, making it the most frequent early molecular genetic alteration in type 1 endometrial tumors, which are generally associated with hyperplasia. p53 gene mutation is not found in endometrial hyperplasia, but researchers have detected this mutation in 20% of cases of endometrial carcinoma and 90% of cases of serous endometrial tumors. Cyclooxygenase-2 is important in tumorogenic transformation of hyperlasia. Expression of cyclooxygenase-2 decreases apoptosis, increases angiogenesis, and is related to invasiveness. Cyclooxygenase-2 expression increases significantly in cases of well-differentiated endometrial adenocarcinoma. Prostaglandin E-2 is known to regulate aromatase gene expression and is the product of cyclooxygenase-2. The data about aromatase inhibitors are promising; in breast cancer patients, treatment with tamoxifen induces uterine abnormalities as early as 3 months after the initiation of therapy. In contrast, these abnormalities are not seen in patients who receive aromatase inhibitors and switched therapy after tamoxifen withdrawal may reverse tamoxifen-associated endometrial thickening.