子宫内膜癌组织中uPA及Cath-D的表达及意义(英文)

目的:检测子宫内膜癌组织中尿激酶型纤溶酶原激活物(uPA)及组织蛋白酶(Cath-D)的表达并探讨相关性及其临床意义。方法:采用免疫组织化学方法(PV-6000二步法)检测31例子宫内膜癌组织(内膜癌组),17例子宫内膜增生组织(增生组)及10例正常子宫内膜组织(对照组)中uPA及Cath-D的表达,并研究其相关性。结果:1.内膜癌组中uPA和Cath-D的表达均高于增生组及对照组中的表达,差异均有统计学意义(P0.05);在增生组中的表达与对照组差异无统计学意义(P0.05)。2.uPA和Cath-D的阳性表达与子宫内膜癌的临床病理分期、组织学分级及肌层浸润深度有关,差异均具有统计学意义(P0.05)。3.内膜癌组中uPA与Cath-D的表达呈正相关(r=0.673,P0.05)。结论:uPA和Cath-D在子宫内膜癌发生发展及侵袭转移过程中起着协同作用,Cath-D可诱导产生活化的uPA,促进癌细胞的浸润转移,因此,两者的联合检测可有助于成为判断子宫内膜癌的发展及预后的重要指标。     

Relations between bleeding pattern,endometrial histology,and oestrogen treatment in menopausal women

Vacuum curettage was performed on 348 women who had received various regimens of oestrogen treatment for an average of 9·7 months for climacteric symptoms. In 62 cases (18%) the specimens were unsatisfactory for histological assessment; among the remainder, however, they showed a normal endometrium in 257 cases (90%), cystic hyperplasia in 21 (7%), adenomatous hyperplasia in 7 (2%), and endometrial adenocarcinoma in one. Cyclical unopposed oral oestrogen treatment (98 cases) was associated with a 12% incidence of endometrial hyperplasia, but among those given an additional five-day course of progestogen in each cycle (37 cases) the incidence was only 8%. No case of hyperplasia occurred among 102 women taking regimens including 10 or 13 days of progestogen. Among women treated with subcutaneous oestradiol implants and monthly five-day courses of oral progestogen (50 cases) there was a 28% incidence of hyperplasia including the one case of carcinoma, though some of those with hyperplasia may not have taken the full course of progestogen. Regular withdrawal bleeding during treatment was associated with a lower incidence of endometrial hyperplasia (6%) than unscheduled breakthrough bleeding (28%), but the one patient with carcinoma had experienced regular bleeding only.The risk of developing endometrial carcinoma from oestrogen treatment may be reduced by avoiding the use of unopposed oestrogen regimens, the addition of more than five days'' treatment with a progestogen, and recognising that a regular bleeding response to oestrogen is no guarantee of a healthy endometrium.     

P63在子宫内膜样腺癌的表达及意义

目的检测正常子宫内膜、子宫内膜增生症和子宫内膜样腺癌（endometriod adenocarcinoma,EC）组织中P63的表达,探讨P63与子宫内膜样腺癌发生、发展及预后的关系。方法采用免疫组化SP法检测正常子宫内膜（20例）,子宫内膜增生症（20例）,子宫内膜样腺癌（50例）组织中P63蛋白的表达。结果（1）正常子宫内膜中仅1例增生期内膜中有P63表达,阳性细胞零星分布于极个别腺体的基底部。子宫内膜增生症和子宫内膜样腺癌组织中,P63阳性细胞常相对集中分布于某一区域的腺体或实性巢,染色强。（2）EC组和子宫内膜增生症组P63的阳性率分别为46％和50％,与正常子宫内膜组（5．0％）比较差异有显著性护〈0．05）。子宫内膜增生症组P63的阳性率与EC组比较差异无显著性（P〉0．05）。（3）P63的表达与EC的分化程度无关（P〉0．05）。结论（1）EC组织中P63阳性细胞可能来源于胚胎时期的未分化细胞,具有多向分化的潜能。（2）P63与EC的发生发展有关,可能起癌基因的作用。（3）P63在子宫内膜增生症组织中高表达,表明P63与子宫内膜的异常增生相关。     

An alternative to the diagnostic dilatation and curettage--endometrial cytology.

Endometrial aspiration cytology has been shown by multicentre prospective studies to be an acceptable and valuable method of assessing the endometrium. A retrospective study was undertaken over three years'' routine use of the Isaacs cell sampler. In 86% of the cases suitable endometrium was obtained, with experience of the technique being the important factor. When compared with histological findings, all 11 cases of malignancy were confirmed, including one ovarian adenocarcinoma. Of the cytological reports of endometrial hyperplasia, 78% were confirmed by the histological findings, with the remainder showing minor degrees of cystic hyperplasia or normal endometrium. In no case was a more abnormal lesion present on histological examination than had been suggested by cytological findings. The use of progestogens in reversing hyperplasia is seen to be effective, though the long term benefit remains uncertain. It is concluded that with an experienced cytologist, Isaacs endometrial aspiration should be used routinely for the primary investigation of dysfunctional uterine bleeding and postmenopausal bleeding.     

A karyometric approach to the characterization of atypical endometrial hyperplasia with and without co-occurring adenocarcinoma

OBJECTIVE: To develop a karyometric image analysis approach to distinguishing atypical endometrial hyperplasia with and without co-occurring adenocarcinoma. STUDY DESIGN: Six cases of atypical hyperplasia without and 6 cases with co-occurring adenocarcinoma, 4 cases of normal endometrium and 3 cases of adenocarcinoma were identified. From each case 100 nuclei were measured in representative diagnostic areas identified by an experienced pathologist. Discriminant analyses were performed. An unsupervised learning algorithm was applied to define and characterize different nuclear phenotypes, and those data were used to identify cases with co-occurring adenocarcinoma. RESULTS: Discriminant analysis showed that nuclei from atypical hyperplasia and atypical hyperplasia with co-occurring adenocarcinoma are statistically different. The unsupervised learning algorithm revealed differences in nuclear subpopulations that can be used to correctly identify an estimated 85% of individual cases. CONCLUSION: Nuclei from atypical hyperplasia without and with co-occurring adenocarcinoma have statistically different karyometric characteristics that may facilitate case classification.     

Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations

Background

Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability. Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases.

Methods

A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS).

Results

The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement). Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined. Interobserver agreement was in substantial rate for simple hyperplasia (SH) and well differentiated adenocarcinoma (WDA) but was in fair limit for complex hyperplasia (CH) and atypical hyperplasia (AH). Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH) ( D Score ≥ 1 or VPS ≥ 55%) and Endometrial Intraepithelial Neoplasia (EIN) (D-Score < 1 or VPS < 55%). Morphometric findings were closely compatible with routine WHO classification made by one expert pathologist; however; diagnosis of (CH) and (AH) made by other pathologists were not concordant with morphometric data.

Conclusion

It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and precancerous lesions.     

Potential of the learning vector quantizer in the cell classification of endometrial lesions in postmenopausal women

OBJECTIVE: To investigate the potential of artificial neural networks for cell identification in endometrial lesions from postmenopausal women. STUDY DESIGN: The study was performed on cytologic material obtained by the Gynoscann endometrial cell samplerfrom 12 cases of atrophic endometrium, 48 cases of hyperplasia without cytologic atypia (18 cases of simple hyperplasia and 30 cases of complex hyperplasia), 12 cases of hyperplasia with cytologic atypia (complex atypical hyperplasia) and 48 cases of adenocarcinoma (30 cases of well-differentiated, 12 cases of moderately differentiated and 6 cases of poorly differentiated carcinoma). From each case approximately 100 cells were examined using a custom image analysis system. A learning vector quantizer (LVQ) identified the collected data. RESULTS: Investigation of cells from Endometrial Alterations with LVQ proved that according to the nuclear characteristics, as expressed by morphometric and textural measures, the endometrial cells from postmenopausal women may be identified as belonging to one of thefollowing three groups: atrophy, hyperplasia without cytologic atypia (simple and complex hyperplasia) and malignant neoplastic lesions (atypical complex and adenocarcinoma). CONCLUSION: The role of nuclear morphologic features in the cytologic diagnosis of endometrial alterations was confirmed. The overlap in thefeature space observed indicates that cell characteristics do not form strictly separate clusters. Thatfact explains the difficulty that morphologists have with the reproducible identification of cells from endometrial lesions in postmenopausal women. Application of LVQ offers a good classification at the cell level and promises to be a powerful toolfor classification on the individual patient level andfor the clarification of the natural history of endometrial pathology.     

Effects of tamoxifen on the endometrium and its mechanism of carcinogenicity

This study was conducted to clarify the clinicopathological characteristics of tamoxifen-associated endometrial carcinomas and its mechanisms of carcinogenesis. Seven patients with tamoxifen-associated endometrial carcinomas (TAM group) and 28 with sporadic endometrioid adenocarcinomas (EMC group) were included in the study. The clinicopathological factors, such as FIGO stage, histological type, grade, lymph node metastases, vascular invasion and the coexistence of hyperplasia, were investigated in both groups. The protein expression of p53, PTEN, hMLH1 and hMSH2 was investigated by immunohistochemistry. Microsatellite instability (MSI), k-ras and p53 mutation were also examined. In the TAM group, the histological types included five endometrioid, one endometrioid combined with serous and one clear cell type. The rates of coexistence with hyperplasia (five of seven cases) and vascular invasion (four cases) were significantly higher in the TAM group. The rates of stage III/IV (four cases) and lymph node metastasis (three cases) tended to be higher in the TAM group. Although there were no significant differences in PTEN, hMLH1 and hMSH2 expression between the two groups, p53 mutation was more frequent in three out of five cases (60%) in the TAM group compared with 2 of 15 cases in the EMC group (13.3%). No significant differences were observed concerning MSI and k-ras mutation in either group. These results suggested that TAM-associated endometrial carcinomas have overlapping biological characteristics of type I and type II endometrial carcinomas. This might explain the somewhat worse prognosis of these tumors than sporadic endometrioid carcinomas.     

Liquid-based endometrial cytology: cyto-histological correlation in a population of 917 women

OBJECTIVE: Liquid-based cytology, because of its capacity to reduce the obscuring factors and to provide thin-layer specimens, represents an opportunity to reevaluate endometrial cytology. In order to assess the utility of the liquid-based method in endometrial diagnosis, we evaluated its accuracy in comparison with histology. METHODS: Nine hundred and seventeen women scheduled for hysteroscopy were enrolled in the study. After providing informed consent, all the women proceeded sequentially to hysteroscopy, endometrial cytology and then biopsy endometrial sampling. RESULTS: Cyto-histological correlations were possible in 519 cases (57%): in 361 (39%) cases the biopsy was inadequate, in 15 (2%) the cytology was inadequate, and in 22 (2%) both were inadequate. At biopsy 25 (3%) women had adenocarcinoma, 5 (1%) had adenomatous atypical hyperplasia and 21 (2%) had simple non atypical hyperplasia. At cytology two adenocarcinomas and one adenomatous atypical hyperplasia were underrated as atypical hyperplasias and as non-atypical hyperplasia; two simple non-atypical hyperplasias were reported as negative; and eight cases were false positive (non-atypical hyperplasia at cytology, negative at biopsy). In our population, the cytology provided sufficient material more often than biopsy (P < 0.04). Sensitivity was estimated at 96%, specificity at 98%, positive predictive value at 86% and negative predictive value at 99%. CONCLUSIONS: We concluded that endometrial cytology may be an efficient diagnostic method. It could be applied to selected patients solely or in association with ultrasonography. The combination of these two noninvasive procedures may improve their diagnostic accuracy and reduce unnecessary hysteroscopies, thereby producing benefits for women and society.     

FAS在子宫内膜样腺癌及其癌前病变中的表达及意义

目的研究脂肪酸合成酶(Fatty acid synthase FAS)在子宫内膜样腺癌及其癌前病变中的表达以及与临床病理意义。方法 37例子宫内膜样腺癌、21例子宫内膜非典型增生、23例子宫内膜复杂性增生、17例子宫内膜单纯性增生及11例增生期子宫内膜中FAS的表达情况,结合临床病理参数并进行统计学分析。结果 FAS在子宫内膜样腺癌、子宫内膜非典型增生、子宫内膜复杂性增生、子宫内膜单纯性增生及增生期子宫内膜中均有表达,其阳性表达率依次为81.1%、57.1%、56.5%、52.9%、45.5%。子宫内膜样腺癌中FAS的阳性表达率明显高于增生期子宫内膜、子宫内膜单纯性增生、子宫内膜复杂性增生及子宫内膜非典型增生(P<0.05)。FAS的阳性表达率在浸润深度≥1/2肌层的子宫内膜样腺癌明显高于浸润深度<1/2肌层者(P<0.05)。FAS的表达与年龄及组织学分级无显著差异性(P>0.05)。在子宫内膜样腺癌中FAS的表达与ER有关(P<0.05)结论本研究提示FAS的表达可能与子宫内膜样腺癌的发生、发展有关。FAS可以作为提示子宫内膜样腺癌预后的一个新的参考指标。部分ER阳性的子宫内膜样腺癌的发生、发展可能与FA...     

人滋养细胞表面抗原（Trop-2）在病变子宫内膜中表达的研究

摘要 目的：探讨人滋养细胞表面抗原（trophoblast cell-surface antigens2,Trop-2）在病变子宫内膜中的表达及其临床相关性。方法：采用免疫组化法检测100例正常子宫内膜或病变子宫内膜组织中Trop-2蛋白的表达,其中单纯增生子宫内膜患者26例,复杂或不典型增生子宫内膜患者34例,子宫内膜腺癌患者20例,对照组为20例增生期子宫内膜患者。结果：免疫组织化学法研究结果显示,Trop-2蛋白在正常增生子宫内膜和单纯性增生子宫内膜中几乎不表达,在复杂或不典型增生子宫内膜组织中以及子宫内膜腺癌呈阳性表达。主要分布在细胞膜上,阳性率分别为35.29 %和65.00 %,经过对比子宫内膜癌组的阳性表达率显著高于复杂型或伴不典型增生子宫内膜组的阳性表达率（P<0.05）,且复杂型或伴不典型增生子宫内膜组的阳性表达率显著高于单纯性增生子宫内膜组（P<0.05）,其表达水平随内膜病变程度的加重而升高,呈正相关关系（P＜0.05）。结论：Trop-2蛋白在子宫内膜病变中的表达与其严重程度一致,可反映子宫内膜病变的发生发展,或可作为判断其严重程度的指标。     

Increasing diagnostic accuracy with a cell block preparation from thin-layer endometrial cytology: a feasibility study

OBJECTIVE: To investigate (1) the feasibility of preparing cell blocks by inverted filter sedimentation (IFS-CB) from endometrial samplings processed by the ThinPrep (TP) technique (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), and (2) the possibility of increasing the diagnostic accuracy of TP endometrial cytology by examining the tissue architecture as an adjunctive method of detecting endometrial lesions. STUDY DESIGN: Three hundred one endometrial samplings were obtained, using the Endogyn endometrial device (Biogyn S. n.c., Italy), from perimenopausal and postmenopausal women. The endometrial samplings were collected in a vial with liquid fixative for the TP processing. One TP slide was prepared from each case. If adequate material remained in the vial after the TP slide preparation, it was processed for IFS-CB preparation. RESULTS: IFS-CB preparation was processed in 263 cases (87%) with adequate material. Diagnoses on IFS-CB preparations obtained by endometrial sampling matched those of the hysterectomy specimens. The addition of IFS-CB histology to the cytologic diagnosis by TP increased the diagnostic accuracy of endometrial cytology to 96.3% and 100% for benign/atrophic endometrium and adenocarcinoma, respectively (p = 0.39 and 0.46). In hyperplasia without atypia and hyperplasia with atypia, the diagnostic accuracy increased significantly, to 96% and 95.3%, respectively (p = 0.037 and < 0.001). CONCLUSION: This study illustrates the merit of linking TP cytology with direct endometrial sampling, including small tissue fragments and material adequate for IFS-CB preparation. TP cytology provides an accurate cytologic diagnosis and the possibility of IFS-CB preparation, which could be a valuable diagnostic adjunct to TP cytology.     

Value of cytology for detecting endometrial abnormalities in climacteric women receiving hormone replacement therapy.

Over six months 113 endometrial specimens from 110 menopausal women receiving hormone replacement therapy were examined by two cytologists and two histopathologists. Specimens were obtained by aspiration with the Isaacs cell sampler immediately before Vabra suction curettage, both procedures being performed in the outpatient department without anaesthetic. The histologists agreed with each other on the classification of 85 specimens (75.2%) and the cytologists agreed on the classification of 44 (38.9%). In only 15 cases (13.3%) did all four observers agree. Of the three cases of cystic or adenomatous hyperplasia detected histologically, only one was diagnosed by cytology. Furthermore, both cases of adenocarcinoma escaped detection by cytology, though a third case--later confirmed-"was suspected by one cytologist alone. Use of the Isaacs endometrial cell sampler cannot be advocated for routine screening of women with climacteric symptoms receiving hormone replacement therapy. Efforts should be made to establish the correct dose and duration of treatment with an oestrogen-progestogen preparation in order to avoid over-stimulating the endometrium and the need for regular screening for endometrial abnormalities.     

凋亡抑制蛋白Survivin在增生性子宫内膜及子宫内膜癌中的表达

目的　研究凋亡抑制蛋白Survivin在正常子宫内膜、增生性子宫内膜及子宫内膜癌中的表达 ,探讨Survivin蛋白在子宫内膜癌发生发展中的作用及其作为预后判断因子的可行性。方法　应用免疫组织化学S P法 ,检测 15例正常子宫内膜、 2 6例增生性子宫内膜及 33例子宫内膜腺癌中Survivin蛋白的表达 ,并结合临床病理特点进行分析。结果　Sur vivin蛋白的阳性表达率在正常子宫内膜 ,增生性子宫内膜及子宫内膜癌中呈上升趋势。正常子宫内膜仅在增生期有微弱的表达 ,而分泌期及绝经期子宫内膜表达全为阴性 ;而Survivin在子宫内膜癌中及不典型增生中的阳性表达率分别为87 88%和 70 0 % ,均明显高于正常内膜 (P <0 0 5 ) ,且两者的过表达率均高于单纯和复合型增生及正常内膜 (P <0 0 5 ) ,但子宫内膜癌中与不典型增生中的Survivin表达率及过表达率均无明显差异。子宫内膜癌中Survivin的表达强度与组织学分级及手术病理分期明显相关 (P <0 0 5 ) ,但与肌层浸润无关。结论　Survivin作为凋亡相关因子和细胞周期调节因子 ,可能参与了与子宫内膜癌的发生发展 ,其过度表达与预后不良相关 ,其检测可为子宫内膜癌的早期诊断、辅助治疗及预后判断提供理论依据。     

DNA image cytometry in the differential diagnosis of endometrial hyperplasia and adenocarcinoma

OBJECTIVE: To test the value of DNA image cytometry in the differential diagnosis of hyperplastic endometrial lesions and endometrial carcinoma on a series of 153 cases of simple hyperplasia (n = 71), complex hyperplasia (n = 28), complex atypical hyperplasia (n = 11) and endometrial adenocarcinoma (n = 43). STUDY DESIGN: Monolayer smears were prepared from three 50-micron-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen randomly, was determined using a TV image analysis system (CM-1, Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every case. Different DNA cytometric parameters and the mean nuclear area were calculated. RESULTS: Cases of adenocarcinoma and complex atypical hyperplasia (n = 54) were defined as clinically "positive" as these patients are normally treated by hysterectomy. The remaining cases of simple and complex hyperplasia (n = 99) were interpreted as clinically "negative" as conservative therapy is usually preferred. Requesting a specificity of > 90%, high sensitivity rates were calculated for ploidy imbalance (94%), mean ploidy (91%), diploid deviation quotient (91%), DNA stemline ploidy (87%) and 2c deviation index (85%), based on suitable thresholds. Entropy (76%), 5c exceeding events (63%), mean nuclear area (48%) and 9c exceeding events (6%) revealed lower sensitivity values. 5c Exceeding events (P = .0117) and mean nuclear area (P = .0392) were helpful in differentiating between atypical hyperplasia and endometrial carcinoma as the data distribution was significantly different with the U test. CONCLUSION: Our results indicate that DNA single cell cytometry is a highly relevant tool in the differential diagnosis of endometrial lesions and could be used as a complementary diagnostic method, especially in histomorphologically difficult cases.     

Cytologic findings in endometrial hyperplasia

The cytologic findings in 15 endometrial hyperplasias were compared with those of normal endometrium and well-differentiated endometrial adenocarcinoma. Differences in tumor diathesis, hypercellularity, uneven internuclear distance, severe piling up of nuclei, anisokaryosis, nuclear size and macronucleoli were the main cytologic findings that were noted among the three conditions. These features varied in the different types of endometrial hyperplasia. It is not clear that these cytologic findings can be used to cytologically diagnose endometrial hyperplasia because some of the findings involve subjective judgments by different cytologists. Further studies on larger series of cases will be necessary to establish the cytologic criteria for the correct interpretation of endometrial abnormalities.     

Endometrial hyperplasia with berrylike squamous metaplasia and pilomatrixomalike shadow cells. Report of an intriguing cytohistologic case

BACKGROUND: The usefulness of endometrial cytology as a diagnostic method in asymptomatic women, especially in postmenopause, in the interpretation of composite pictures characterized by borderline features between atypical hyperplasia and well-differentiated adenocarcinoma, especially if associated metaplastic features are present, is somewhat controversial. CASE: An asymptomatic, 50-year-old, postmenopausal woman underwent a Pap smear and endometrial cytology for routine screening, disclosing three-dimensional, sometimes pseudopapillary groupings of hyperplastic endometrial glandular cells with focal atypia in direct continuity with large, squamoid cells of the keratinizing type and shadow cells. Histologic examination of endometrial tissue was advised, and two subsequent endometrial biopsies and hysteroscopic ablation were performed. The borderline character of the lesion (complex atypical hyperplasia vs. well-differentiated adenocarcinoma) with concomitant squamous metaplasia and pilomatrixomalike shadow cells prevented diagnostic agreement between several pathologists. CONCLUSION: Diagnostic cytology with direct endometrial sampling represents a valuable diagnostic screening tool for the differential diagnosis between normal and pathologic endometrium, a mucosal picture that deserves a subsequent (histologic) diagnostic procedure. In a few cases, as in the one presented above, even histologic examination, especially of so-called borderline lesions, reveals squamous or other types of metaplasia that can lead to interobserver discrepancies.