不同分子学筛查方法在Lynch综合征相关子宫内膜癌患者中的对比分析#br#

Objective?Compare the accuracy of immunohistochemical staining (IHC), microsatellite instability detection (MSI), and the combined detection of the two in the screening of Lynch Syndrome-related endometrial cancer (LS-EC), and analyze the advantages and disadvantages of actual clinical applications, to identify a routine and reasonable screening strategy. This study also reveals the incidence of LS-EC and the mutations of different mismatch repair (MMR) genes in the Chinese population in this region. Methods?IHC MMR protein detection and MSI detection were performed on the pathological tissues of diagnosed EC patients from the Second Hospital of Jilin University from November 2019 to November 2020, and the preoperative venous blood was subjected to next-generation sequencing (NGS) of Lynch syndrome-related mutations. Results?After NGS testing, 8 cases of LS were confirmed, with an incidence rate of 7.90%. 28 cases had lack of expression of MMR protein, 7 cases were diagnosed as LS, 1 case was missed diagnosis; 13 cases had high microsatellite instability (MSI-H), 3 cases were diagnosed as LS, 5 cases were missed; the combined detection of the two tests can screen out all LS patients. Conclusion?IHC combined with MSI screening is highly sensitive but not cost-effective. IHC alone is recommended as the first clinical screening method.     

Experiences with a cytologic method of diagnosing endometrial cancer

A method to gain endometrium cells by lavage of the uterus cavity and subsequent aspiration is shown. The insertion of a 4.0 mm cannula without dilatation couldn't be managed successfully up to 14% of 256 examinations. From 220 washings 18.6% of smears couldn't be commented on. 179 smear preparations were commented and the recognition rate concerning the endometrial carcinoma commented to 69.2%.     

Assessment of reliability endometrial brush cytology in detection etiology of late postmenopausal bleedings

We evaluated the possibility of discovering bleeding causes in late postmenopausal period with cytological examination of material received by endometrial brush in comparison with Pap test and fractionated curettage. Sixty-two women in late postmenopausal period with cervical canal bleeding, treated in gynecological department of clinical hospital in Osijek, were cytological and histological processed. Final diagnosis in 29 from 62 (46.8%) women with late postmenopausal bleeding was cancer. 25 (40.3%) women had endometrial adenocarcinoma and 4 (6.5%) of them had squamous endocervical carcinoma. Two women had endometrial precancerous (3.2%). With Pap test accurate diagnosis was set up in 13 from 25 (52.0%) women with endometrial adenocarcinoma and in all of them with squamous endocervical carcinoma. With endometrial brush accurate diagnosis was set up in 14 from 25 (56.0%) women with endometrial adenocarcinoma and in 3 from 4 (75.0%) women with squamous endocervical carcinoma. With fractional curettage the diagnosis of endometrial adenocarcinoma was accurately correct in 21 from 25 (84.0%) women and in all of them with squamous endocervical carcinoma. Cytological examination of material derived with endometrial brush, alike vaginal cytology, is not enough reliable method in our conditions for discovering bleeding causes in late postmenopausal period. Diagnostic exactness of procedure could be increased by histopathological examination of material from endometrial brush procedure and with ultrasound evaluation of endometrium thickness.An erratum to this article can be found at     

Assessment of prognostic factors in stage IIIA endometrial cancer

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.     

不同雌激素受体表达状态的子宫内膜癌细胞中转录因子的活性分析

目的 分析并比较不同雌激素受体(ER)表达状态的子宫内膜癌细胞中转录因子的活 性.方法 采用实时荧光定量RT-PCR技术检测子宫内膜癌细胞系RL-952[Erα、Erβ表达均阳性(+)]、HEC-1A[Erα表达弱阳性(±)、Erβ表达阴性(-)]、HEC-1B[Erα、Erβ表达均(-)]细胞中Erα mRNA的表达.采用345通量转录因子芯片检测RL-952、HEC-1A、HEC-1B细胞中转录因子的活性,采用酶联免疫吸附试验(ELISA)方法检测不同转录活性的转录因子NFkKBp65、p38MAPK以验证芯片检测结果.结果 Erα mRNA在RL-952、HEC-1A、HEC-1B细胞中表达水平依次递减,分别为(6780±282)、(684±84)、(168±38)copy/ng.转录因子NFkBp65、p38MAPK的转录活性采用ELISA方法检测(分别为2.0±0.4、0.9±0.5,P=0.020)与芯片检测(分别为3003±530、882±538,P:0.017)结果一致.在345个转录因子中,筛选出与ER功能相关的差异表达的转录因子共28个,与ER(+)的RL-952细胞相比,ER(-)的HEC-1A、HEC-1B细胞中转录因子活性同时上调的有13种,同时下调的有15种.转录因子TTF(1)-1、NRF-1、TCE的活性与Erα mRNA表达水平呈明显线性正相关关系(r=0.523,P=0.037),而转录因子RFX123和Ikaros的活性与Erα mRNA表达水平呈明显非线性负相关关系(r=-0.312,P=0.041).结论转录因子芯片检测是筛选子宫内膜癌致病机制中主要转录因子的先进技术.转录因子TTF(1)-1、NRF-1、TCE可能与ER(+)子宫内膜癌中的信号传导通路相关;转录因子RFX123和Ikams可能与ER(-)子宫内膜癌中的信号传导通路相关.     

Ultrasonographic endometrial thickness for diagnosing endometrial pathology in postmenopausal bleeding.

We conducted this retrospective analysis of our clinical data to identify the incidence of benign endometrial abnormalities, endometrial carcinoma and to find out the endometrial thickness (ET) cut-off point using trans-vaginal ultrasonography for patients with postmenopausal bleeding (PMB) referred to the Rapid Access Clinic in Northampton General Hospital. All women referred between April 2004 and April 2005 with PMB were included in this analysis. Final diagnostic outcome was classified into benign endometrial polyp, endometrial hyperplasia, endometrial carcinoma or normal (by excluding these pathologies). A total of 142 patients were included in this survey. The incidence of abnormal endometrial pathology was found to be 23.9% and 5% for endometrial carcinoma. Our results suggested that benign endometrial pathology is the most common cause of postmenopausal bleeding. Lowering the endometrial thickness cut-off point from 5 mm to 3 mm will not improve the diagnostic accuracy of endometrial carcinoma.     

细胞角蛋白、CA125对子宫内膜癌淋巴结微转移的诊断价值

目的　研究细胞角蛋白 (cytokeratin ,CK)、CA12 5对子宫内膜癌淋巴结微转移的诊断价值 ,及其作为子宫内膜癌复发危险因素的临床意义。方法　采用免疫组化链霉菌抗生物素蛋白 过氧化物酶连接 (SP)法检测 5 0例子宫内膜癌患者的原发灶组织 5 0份和淋巴结 2 98枚中CK、CA12 5的表达情况 ,采用多元回归分析法对影响子宫内膜癌复发的危险因素进行分析。结果　 (1)CK、CA12 5在子宫内膜癌组织中的阳性表达率分别为 10 0 % (5 0 / 5 0 )和 78% (39/ 5 0 )。 (2 )HE染色检查有转移的淋巴结中 ,CK和CA12 5均呈强阳性表达的阳性表达率均为 10 0 % (16 / 16 )。HE染色检查无转移的淋巴结中 ,CK、CA12 5的阳性表达率分别为 15 % (4 3/ 2 82 )和 12 % (35 / 2 82 ) ,且均为弱阳性表达。 (3)Ⅰ、Ⅱ期子宫内膜癌患者淋巴结中 ,CK阳性与CK阴性表达者的复发率分别为 38%、0 ,两者比较 ,差异有显著性 (P <0 0 5 ) ;CA12 5阳性与CA12 5阴性表达者的复发率分别为 39%、4 % ,两者比较 ,差异也有显著性 (P <0 0 5 )。 (4 )多元回归分析结果显示 ,淋巴结中CK表达是影响Ⅰ、Ⅱ期子宫内膜癌复发的独立危险因素 ,而淋巴结中CA12 5表达和肌层浸润深度均为影响Ⅰ、Ⅱ期子宫内膜癌复发的相关因素。结论　在HE染色检查无转移的淋巴     

客观评价子宫内膜癌筛查方法

子宫内膜癌发病率上升,高危人群增多,应该高度关注子宫内膜癌筛查,临床上应用的子宫内膜癌筛查方法有子宫内膜脱落细胞学检查、子宫内膜脱落细胞块病理检查和子宫内膜微量组织获取检查。3种方法各有优缺点。目前,尚缺乏理想的子宫内膜癌筛查方法。     

不同期别子宫内膜癌组织中差异表达基因的层次聚类分析

目的探讨对不同期别子宫内膜癌组织中的差异表达基因进行层次聚类分析的意义。方法利用基因芯片技术分析32例不同期别子宫内膜癌组织中的差异表达基因,并对其基因表达谱进行层次聚类分析。结果根据国际妇产科联盟（FIGO）手术病理分期的不同对所有样本进行分组,分为Ⅰ、Ⅱ、Ⅲ、Ⅳ期组4组,筛选出与肿瘤转移相关的差异表达基因12个。根据这12个差异表达基因对32例内膜癌进行层次聚类分析,其结果与手术病理分期的符合率为66％。结论基因芯片技术可以发现与子宫内膜癌转移相关的差异表达基因,基因表达谱层次聚类分析可以在术前帮助判断高危型子宫内膜癌。     

Prognostic significance of different therapeutic procedures in stage I endometrial cancer

The prognostic importance of the different lines of therapeutic management are retrospectively reviewed from 230 patients who have been primarily operated on for endometrial carcinoma stage I (FIGO). The postoperative radiation therapy taking into consideration the prognostic significance of the tumour criteria (tumour type, degree of differentiation and extent of myometrial invasion) as well as the age and the general condition of the patient would largely be individualized. 56 (24%) patients has been operated on only. There were no significant prognostic differences for vaginal and abdominal hysterectomies with bilateral salpingo-oophorectomy. Extensive operative measures have been carried out seldom and could not yet be included in the evaluation. A simultaneous gestagen administration in 39 (17%) of the cases with invasively growing carcinomas (greater than 1/3 myometrial invasion), independent from the previous therapeutic regimen, is shown not to have improved the healing results. The favourable prognosis of women mostly with lower primary risk and operated on only as opposed to postoperatively radiated ones underlines the primary prognostic significance of morphological characteristics of the tumour although no definite conclusions can be derived from the concurrent effectivity of the adjuvant radiotherapy for early tumour stages. A postoperative radiation therapy, because of its late consequences which have been observed during tumour follow up, is indicated only in those cases with unfavourable prognostic criteria.     

细胞学联合组织学在子宫内膜病变无创筛查中的应用价值

目的:探讨联合应用组织学及细胞学的方法筛查子宫内膜病变的临床应用价值。方法:选取62例有异常阴道出血或B超提示子宫内膜异常需行诊断性刮宫的妇女,术前使用一种特制的带有负压吸引装置的子宫内膜取样器进行宫腔细胞学采样,将细胞学及无创组织学的结果与诊断性刮宫后病理结果比较,分析其取材满意度、诊断符合率、出血量及疼痛程度。结果:子宫内膜取样器取材满意率为98.4%,细胞学诊断的敏感性、特异性及符合率分别达到83.3%、93.9%和91.8%;子宫内膜取样器中组织物获得率91.9%,通过取样器获得组织学的患者与其细胞学联合,诊断敏感性、特异性及准确率达到84.6%、95.8%和93.4%。子宫内膜取样器取材操作中出血量平均为(1.2±0.9)ml;诊断性刮宫取材满意率为100%,出血量平均为(6.3±8.3)ml。结论:可通过子宫内膜取样器获得子宫内膜的宫腔细胞学及组织学标本,从而做到简单、安全、可靠地筛查子宫内膜病变。     

Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis

Our aim was to determine the diagnostic accuracy of endometrial thickness measurement by pelvic ultrasonography for predicting endometrial carcinoma and disease (hyperplasia and/or carcinoma) during an investigation of postmenopausal bleeding. We performed a systematic quantitative review of the available published literature, which consisted of online searching the MEDLINE and EMBASE databases (1966-2000) coupled with scanning of bibliography of known primary and review articles. The selection of studies, assessment of study quality, and extraction of data were performed in duplicate under masked conditions. Included in the analyses were 57 studies with 9031 patients. Accuracy data were summarized using likelihood ratios for various cut-off levels of abnormal endometrial thickness. The commonest cut-offs were 4 mm (9 studies) and 5 mm (21 studies), measuring both endometrial layers. None of the nine studies using the < or = 4 mm cut-off level were of good quality. Only four studies (out of the 21) used the < or = 5 mm cut-off level, which employed the best-quality criteria. Using the pooled estimates from these four studies only, a positive test result raised the probability of carcinoma from 14.0% (95% CI 13.3-14.7) to 31.3% (95% CI 26.1-36.3), while a negative test reduced it to 2.5% (95% CI 0.9-6.4). In conclusion, ultrasound measurement of endometrial thickness alone, using the best-quality studies cannot be used to accurately rule. However, a negative result at < or = 5 mm cut-off level measuring both endometrial layers in the presence of endometrial pathology rules out endometrial pathology with good certainty.     

治疗方法对子宫内膜癌患者生活质量影响的初步探讨

目的 了解治疗后子宫内膜癌患者的生活质量,比较不同的治疗方法对其生活质量的影响,为临床选择个体化治疗方案提供参考.方法 随访2002年1月至2008年12月于北京大学人民医院手术治疗的子宫内膜癌患者,评估并比较经不同方法治疗的患者生活质量.结果 Ⅰ期及未合并其他恶性肿瘤的子宫内膜癌患者,接受手术+内分泌治疗者(n=87...