PROGINS receptor gene polymorphism is associated with endometriosis

OBJECTIVE: To investigate the association between the 306-base pair insertion polymorphism in intron G of the progesterone receptor (PROGINS) and endometriosis. DESIGN: Case-control study. SETTING: Tertiary care center. PATIENT(S): Ninety-five white women with surgically diagnosed and histologically confirmed endometriosis and 107 white women without endometriosis (controls). INTERVENTION(S): Determination of PROGINS was performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and distribution of the PROGINS allele. RESULT(S): Frequencies of the mutant allele T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio, 2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women with endometriosis and 0.9% of controls. CONCLUSION(S): PROGINS appears to be associated with endometriosis in white persons.     

新生儿硬肿症并肺出血36例临床分析

目的 评价孕酮受体基因内含子G插入306碱基对多态性（PROGINS）在子宫内膜异位症发病中的意义。方法 2005-06—2006-06中国医科大学附属二院和解放军463医院将66例手术及组织学证实诊断的子宫内膜异位症患者和非子宫内膜异位症对照组56例，通过人末梢血提取白细胞DNA，PCR检测基因型分布频率及等位基因（野生型T1和突变型T2）频率．结果 两组比较突变型T2基因型分布频率分别为子宫内膜异位症组0．14，对照组0．04，OR：4．54（95％C1：1.50—13.78），P=0.004。子宫内膜异位症组有2例纯突变型T2（3．0％）：结论 PROG1NS可能与子宫内膜异位症发病有关。     

抗孕激素药物敏感性与孕激素受体基因多态性关系的研究

目的:研究孕激素受体基因多态性与抗孕激素药物敏感性的关系。方法:辽宁省部分地区因非意愿妊娠要求药物流产孕妇185例,根据对药物的临床反应情况将其分成正常完全流产组、敏感组、不全流产组及失败组并进行血清激素水平测定;采用PCR-SSCP方法筛查孕激素受体基因上具有遗传学意义的3个单核苷酸多态性位点(G1031C Ser344Thr;G1978T Leu660Val;C2310T His770His)在各组中的分布情况。结果:PCR扩增的DNA片段经变性成单链,并进行电泳后,各组显示的条带完全一致,说明3个SNP位点在各组中的分布不存在差异。结论:这3个孕激素受体基因的SNP位点在所调查的辽宁省女性中对于抗孕激素药物反应敏感性的影响没有统计学意义。     

Progesterone and endometrial cancer

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.     

基质金属蛋白酶-2及孕激素受体在子宫内膜癌组织中的表达及其意义

目的检测基质金属蛋白酶-2（MMP-2）和孕激素受体（PR）在子宫内膜癌组织中的表达，分析其在子宫内膜癌中表达的相关性以及与临床病理特征的关系，探讨MMP-2在子宫内膜癌发生、发展中的作用。方法采用免疫组化SP法检测45例子宫内膜癌和12例增生子宫内膜中MMP-2、PR的表达，以20例正常子宫内膜作为对照。结果MMP-2蛋白在正常子宫内膜、增生子宫内膜中的阳性表达率比较，差异无显著性（P〉0．05）。子宫内膜癌组织中MMP-2阳性表达率（62．2％）高于对照组（15．6％）（P〈0．05）。MMP-2在中、低分化子宫内膜癌组织中的阳性表达率（82．6％）高于高分化子宫内膜癌组织（40．9％）（P〈0．01），有肌层浸润标本中的阳性表达率（71．1％）高于无肌层浸润者（14．3％）（P〈0．05）；绝经者（65．5％）与未绝经者（56．3％）、手术病理为Ⅰ期者（52．0％）与Ⅱ～Ⅳ者（75．0％）以及有淋巴结转移者（63．6％）与无淋巴结转移者（61．8％）相比，MMP-2的阳性表达率差异无显著性。子宫内膜癌中PR的阳性表达率（55．6％）明显低于对照组（84．4％）（P〈0．05）。MMP-2与PR在子宫内膜癌中的表达呈负相关（P=0．0048，r=-0．42）。结论MMP-2在子宫内膜癌中呈高表达，可能在其进展中有重要作用，PR表达降低可能是MMP-2表达升高的原因；检测MMP-2在子宫内膜癌中的表达，有助于子宫内膜癌预后的判断。     

Utility of MIB-1 and estrogen and progesterone receptor in distinguishing between endometrial stromal sarcomas and endometrial stromal nodules, highly cellular leiomyomas

It is difficult to differentiate between an endometrial stromal nodule (ESN) and endometrial stromal sarcoma (ESS) in curettage specimen, and the recommended therapy of endometrial stromal neoplasm is hysterectomy. If we could discriminate ESS from ESN in curettage specimens, there would be an opportunity to treat ESN by local excision rather than by hysterectomy. We analyzed MIB-1 and estrogen and progesterone receptor (ER/PR) expression in a retrospective series of 8 ESSs, 7 ESNs, and 17 highly cellular leiomyomas obtained from hysterectomy specimens. ESSs expressed MIB-1 more frequently than ESNs (P < 0.05), and ESSs had a tendency to express ER less frequently than ESNs (P= 0.08). We observed that in spite of showing MIB-1 expression to some extent, highly cellular leiomyomas usually could not reach ESSs' level and frequency of MIB-1 expression in the current study. Although MIB-1 and ER appear to be promising markers in the differential diagnosis of ESSs, a larger study would be necessary to confirm their validity.     

子宫内膜癌流行病学及发病因素

子宫内膜癌是女性生殖道三大恶性肿瘤之一,在欧美国家其发病率已占妇科恶性肿瘤的第一位。近年来,包括我国在内的许多发展中国家经济高速发展,人们生活习惯及饮食结构西方化,肥胖人群增多,以及非正规的激素替代治疗等多种因素导致内膜癌发生率明显上升,成为严重威胁发展中国家女性健康的生殖道恶性肿瘤。内膜癌的高危因素包括单纯雌激素的长期刺激、肥胖、糖尿病、高血压、不孕和绝经延迟等。     

Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient.     

Immunohistochemical determination of estrogen and progesterone receptors and DNA flow cytometry in endometrial cancer

Estrogen and progesterone receptor contents (ER, PR) were assessed by an immunohistochemical method and DNA ploidy and S-phase by flow cytometry in frozen endometrial cancer tissue sections from 39 cases. Comparison of the immunohistochemical and cytosol assays showed 81% and 84% concordance in ER and PR contents, respectively. An aneuploid DNA pattern was identified in 30% and a high S-phase fraction was found in 33% of 36 specimens studied. Negative ER status was associated with aneuploid and high S-phase fraction. A similar association was found between PR status and high S-phase fraction. Combined analysis of immunohistochemical receptor status and DNA flow cytometry in the same sample makes it possible to identify two strong predictive factors in endometrial adenocarcinoma.     

子宫内膜癌保留生育功能的治疗

未生育的年轻子宫内膜癌患者常常寻找保留生育功能的治疗方法。本文的主要目的是复习有关子宫内膜癌患者保留生育功能治疗的相关文献,探讨适合进行保留生育功能治疗的患者特征、治疗前的评估、治疗方案、疗效以及妊娠率。     

雌激素对子宫内膜癌孕激素受体亚型调控的研究

目的 研究不同剂量雌激素(雌二醇,E_2)对子宫内膜癌细胞系中孕激素受体亚型在蛋白水平的调控,探讨雌激素、孕激素受体亚型与子宫内膜癌的关系。方法 体外培养子宫内膜癌细胞系HEC-IB,分别用含5nm、10nm、20nm雌二醇的培养液分别作用于细胞24、48、72h,以不含雌二醇的培养液培养细胞为自身对照。通过Western blot方法观察不同剂量雌激素对孕激素受体亚型A、B的蛋白水平调控的动态变化,并以乳腺癌细胞系MCF-7为对照。结果 ①HEC-IB细胞分别经5nm、10nm、20nm的E_2作用24、48、72h后,与未加药的细胞相比,不同浓度、时间下E_2对hPRB调控作用均不明显;而对hPRA的作用在E_2 5um时下调,且随时间延长,下调作用越加明显;在10nm的第24、48h下降,其后渐上升,而在E_2 20nm作用72h时基本恢复加药前的水平。②MCF-7细胞分别经E_2 5nm、10nm、20nm作用24、48、72h后,与未加药的细胞相比较,各种浓度及时间下,E_2对hPRA、B有上调作用的趋势;其中10nm的E_2上调作用较为明显,各种浓度的E_2在第48h的上调作用更为显著。结论 E_2对hPR亚型的调控具有细胞特异性、时间及剂量的依赖性。HEC-IB细胞中,各种浓度、时间下E_2对hPRB调控作用均不明显;而对hPRA的调控作用具有下调的趋势。     

Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk

OBJECTIVES: MDM2 is an important negative regulator of the p53 tumor suppressor protein. A naturally occurring T/G single nucleotide polymorphism (SNP) in the MDM2 gene promoter, SNP309, causes an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity. SNP309 occurs at a relatively high frequency in the general population and has been associated with accelerated tumorigenesis in hereditary Li-Fraumeni associated cancers as well as in sporadic soft tissue sarcomas. The objective of this study was to examine the association between SNP309 and sporadic endometrial cancer risk. METHODS: Genomic DNA was isolated from 73 patients with endometrial cancer and 79 healthy, female controls. The MDM2 gene promoter region was amplified by PCR and the SNP309 genotype determined by restriction enzyme digestion of the amplified DNA fragment. Unconditional logistic regression analysis was used to determine the relationship between genotypes and endometrial cancer risk and histopathologic features. RESULTS: The homozygous G/G genotype was found in 25% of endometrial cancer cases and 11% of controls. In an age-adjusted analysis of cases and controls, the G/G genotype increased the risk of endometrial cancer 2.76-fold (95% CI: 1.06, 7.20; p=0.03) compared to presence of a wild-type T allele (T/G and T/T genotypes). No association was found between the SNP309 G/G genotype and either endometrial cancer histology, grade, stage, or age at diagnosis. CONCLUSIONS: The MDM2 SNP309 homozygous G/G genotype may be a genetic variant that influences sporadic endometrial cancer susceptibility.