子宫内膜癌PTEN蛋白表达及其临床意义

目的 :探讨抑癌基因第 10染色体同源丢失性磷酸酶 -张力蛋白基因 (PTEN)蛋白表达与子宫内膜癌的发生、发展及复发的关系。方法 :采用免疫组织化学S P法检测PTEN蛋白在 5 0例子宫内膜癌、12例不典型增生子宫内膜及 10例正常子宫内膜组织的表达。结果 :5 0例子宫内膜癌中PTEN蛋白表达率为 5 6 0 0 % ,明显低于正常子宫内膜以及不典型增生子宫内膜中的表达 (10 0 0 0 %、91 0 0 % ) (P <0 0 5 )。PTEN蛋白在无肌层浸润或肌层浸润≤ 1/ 2的子宫内膜癌中阳性表达率为 76 0 0 % ,肌层浸润 >1/ 2或有淋巴结转移者为 36 0 0 % ,与肌层浸润程度显著相关 (P <0 0 5 ) ,且Ia Ib期与Ic期相比也有统计学差异 ;但与子宫内膜癌的组织学分级、有无复发无关 (P >0 0 5 )。结论 :抑癌基因PTEN蛋白表达缺失在子宫内膜癌的发生、发展、浸润及复发过程中有一定作用。     

CA125与子宫内膜抗体测定用于诊断子宫内膜异位症

测定了４２例妇女血清和腹腔液ＣＡ＿（１２５）及子宫内膜抗体（ＥＭＡｂ）水平，其中经腹腔镜诊断为子宫内膜异位症者２８例（观察组），无子宫内膜异位症者１４例（对照组）。结果表明：观察组血清ＥＭＡｂ的吸光度为０．４４±０．１３，明显高于对照组的０．３４±０．０７，但两组间血清ＣＡ＿（１２５）差异无显著性；两含用于诊断的敏感性分别为７１．４３％和８２．１４％，特异性为５７．２１％和５７．１４％。两组腹腔液中ＥＭＡｂ差异无显著性；两组腹腔液ＣＡ＿（１２５）和ＥＭＡｂ水平均明显高于血清。     

Heparanase expression increases throughout the endometrial hyperplasia-cancer sequence.

OBJECTIVE: To assess the expression of heparanase in the different stages leading to endometrial cancer. METHODS: The 38 examined specimens included adenocarcinoma, hyperplasia, and normal endometrium specimens. Heparanase, estrogen, and progesterone receptor expressions were analyzed immunohistochemically and the intensity was scored. RESULTS: Secretory normal endometrium and simple hyperplasia specimens expressed the lowest mean values of expression (1.00 and 0.63, respectively); the complex hyperplasia specimens and G2 endometrioid adenocarcinoma showed the highest values of expression (2.33 and 2.71, respectively). A linear trend (P=0.005) of heparanase expression was observed when comparing the normal endometrium and simple hyperplasia group with the complex hyperplasia+G1 carcinoma group and the G2+G3 carcinoma group. Evaluation of atrophic and inactive endometrium compared with papillary serous carcinomas yielded no significant differences. We found no significant correlation between heparanase expression and estrogen receptor or progesterone receptor expression. CONCLUSION: Heparanase expression was tightly regulated in endometrial tumorigenesis.     

代谢组学在妇科常见肿瘤治疗和预后评估中的应用

卵巢癌、子宫内膜癌和宫颈癌是妇科常见的三大恶性肿瘤,尽管随着手术、放化疗等综合治疗的不断发展,妇科常见恶性肿瘤患者的预后得到了大幅提升,但由于早期没有明显症状且缺乏准确诊断或发现时已是晚期,仍有相当比例的患者预后不佳,生命受到严重威胁。因此,寻找新的治疗靶点和监测疗效的有效标志物至关重要。代谢组学（metabonomics）是肿瘤研究领域颇受关注的研究方法,其理论基础是肿瘤存在有别于正常组织的代谢特征,肿瘤独特的代谢特征与生物表型存在紧密的关联。代谢组学通过对生物系统中内源性代谢物进行全面分析,阐明肿瘤在发生和进展过程中某些关键生化途径的重塑机制,并对其进行解析与精准干预。综述代谢组学在妇科常见肿瘤治疗和预后评估中的应用,预期其可为妇科常见肿瘤的个性化、精准化治疗提供潜在靶点,为妇科常见肿瘤筛选预后生物标志物提供重要参考。     

富血小板血浆在妇科疾病治疗中应用及其研究现状

富血小板血浆(PRP)是人自体全血经离心后获得的血小板浓缩物,含有大量生长因子及蛋白质。PRP因其有助于组织再生、伤口愈合、瘢痕修复等作用,在骨科、皮肤科、口腔颌面外科、整形美容科等领域应用广泛,而在妇科领域应用迄今相对较少。最新研究结果显示,PRP具有促进子宫内膜和卵泡生长作用,在治疗薄型子宫内膜(TE)、改善子宫内膜容受性(ER)、恢复卵巢功能等方面取得较大进展,并为多种妇科疾病治疗提供新的研究方向和手段。笔者拟就PRP的制备及分类、在妇科疾病治疗中的应用及其前景展望等最新研究现状进行阐述。     

The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.