Search

The normal endometrium has a wide spectrum of appearances according to the patient’s age and phase of menstruation; understanding this variability is essential in differentiating normal entities from pathologic processes that may require further workup.

Endometrial cancer risk is more strongly associated with obesity than any other cancer type and it is estimated that well over half of endometrial cancer cases in the US are attributable to being overweight and obese. The evaluation of new therapeutic regimens for the prevention and treatment of human endometrial cancer patients is dependent on the development of relevant preclinical models. This chapter will examine the animal models available for endometrial cancer studies in the lab, with a focus on mouse models. Mice and other rodents represent the front line for early preclinical studies in cancer research. We will discuss specific mouse models of endometrial cancer and will further present techniques that can be used to study the role of diet, obesity, and exercise on the normal endometrium and on the pathogenesis of endometrial cancer in the lab.

It is widely known that an adequate growth of the endometrium is indispensable for implantation and successful pregnancy. However, there is no clear agreement on what proper growth is. When reviewing the literature, it is accepted that an endometrial thickness of less than 7 mm would be considered as a refractory endometrium (or thin endometrium) and that would entail to altered pregnancy and live birth rates [1, 2]. It has been long tried to define the optimal characteristics of that “ideal” endometrium in which to transfer the best possible embryo. Investigators have sought to determine it using ultrasonography regarding its thickness and its pattern, but no explicit agreement has been established to date. Moreover, pregnancies and live births have been documented both with thinner and normal endometrium [3]. Therefore, because of the difficulties in defining diagnostic criteria, it is challenging to calculate its true prevalence, although some researchers estimate it around 2.42% (260/10724 women) [4].

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

The genesis of the endometrial polyp is as yet unclear. There is evidence that the polyp is related to the inflammatory process and that it interacts with the cyclooxygenase-2 (COX-2) enzyme.To review the influence of COX-2 on the postmenopausal endometrial polyp.A systematic review was made of the Medline, Embase, and Cochrane databases, covering the years of 2001-2014. The inclusion criteria were: experimental studies with immunohistological analysis of COX-2 in endometrial polyps; women; hysteroscopic and surgical evaluation; and studies with comparisons between the endometrial polyp and other tissues (normal endometrium, adjacent endometrium, and other uterine diseases). The exclusion criteria were: polyps in other organs; genetic polymorphisms; endometrial cancer exclusively; abnormal uterine bleeding unrelated to polyps. The search key words (taken from the Medical Subject Headings - MeSH) were endometrial polyp and cyclooxygenase-2.Seven of ten articles were selected. Results showed positive COX-2 expression in the glandular epithelium of the polyps, and expression was more intense when the polyp was malignant. However, there was a study which did not find any difference between polyps and the normal endometrium, and there was another which compared polyps in menacme with postmenopausal polyps.There is no consensus in the literature as to the participation of COX-2 in the development of benign and/or malignant endometrial polyps. In all of the studies, COX-2 was present in the postmenopausal polyps and with greater intensity in the malignant ones.

The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. DNA methylation of the NOX4 promoter was determined by means of MethyLight PCR. Data were correlated with clinicopathological parameters and analyzed in the context of diabetes and body mass index. In the normal endometrium, NOX4 microRNA expression was significantly higher in the secretory transformed compared with proliferative endometrium ( p = 0.008). In endometrial cancer specimens, NOX4 expression did not differ between diabetic and non-diabetic patients, but was the highest in patients with a body mass index ≤ 26 ( p = 0.037). The lowest NOX4 expression was found in carcinosarcomas ( p = 0.007). High NOX4 expression predicted poorer clinical outcome with regard to overall survival, especially in non-diabetic patients and those with a body mass index > 20. Independent prognostic significance of NOX4 transcripts was retained in type I endometrial cancer and was the most meaningful in patients with a body mass index > 20. No prognostic impact was shown for NOX4 promoter methylation in endometrial cancer. For the first time, we demonstrate that NOX4 plays a considerable role in the cycle-dependent changes in the normal endometrium and in the biology of endometrial cancer.

Objective To evaluate sonohysterography for the diagnosis of endometrial abnormalities in women treated with tamoxifen for breast cancer. Patients and methods We assessed 37 women treated with tamoxifen for breast cancer who underwent sonohysterography and correlative endometrial biopsy for evaluation of postmenopausal bleeding or thickened endometrium greater than 8 mm. In 14 patients, endometrial biopsy was followed by endovaginal sonography to ensure removal of endometrial pathology. Sonohysterography findings were compared with histopathology results. Results Sonohysterography findings coincided with histopathology results in 27 of 37 cases including 19 of 23 cases of endometrial polyps, 6 of 8 cases with thickened endometria and two cases had normal endometrium. Sonohysterography findings did not coincide with histopathology in 3 of the 14 cases who underwent endovaginal sonography after endometrial biopsy compared to 7 of the 23 cases who did not undergo such examination and 4 of these missed 7 cases were for endometrial polyps. Conclusion Sonohysterography is a useful procedure for the diagnosis of endometrial abnormalities in tamoxifen-treated women. Endometrial abnormalities are better diagnosed on sonohysterography than on endometrial biopsy which has the limitation of some missed endometrial polyps, a problem that may be minimized by performing endovaginal sonography after endometrial biopsy.

Aims It has been reported that the expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1), which synthesizes the core 2 branching structure on O-glycans, may be associated with the biological aggressiveness of tumour cells. Therefore, the aim of this study was to examine the relationship between the expression of C2GnT1 and clinicopathological parameters of patients with endometrial carcinoma. Methods and results The immunohistochemical expression of C2GnT1 was examined in 84 cases of endometrioid-type endometrial carcinoma, 15 cases of endometrial hyperplasia, and 30 normal endometria. The staining intensity was reported according to a positivity index (PI, full score 100), calculated from the percentage of positive cells. The expression of C2GnT1 was significantly higher in endometrial carcinoma (PI = 8.31 ± 15.29) than in normal endometrium (PI = 0.52 ± 1.24) (P

Purpose To evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC). Methods The study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS). Results In EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE (p

Objective: To evaluate whether or not the liquid-based procedure (LBP) for endometrial cytology is as worthwhile for endometrial phasing as conventional slides. Materials and Methods: The subjects were 81 women who underwent endometrial cytology and were defined as negative. The specimens obtained by either Endocyte® or Masubuchi aspiration tube® were processed first with the conventional procedure and then with LBP using TACAS™. Results: (1) The number of subjects diagnosed by the conventional method as having proliferative, mid-, middle-secretory and late-secretory and atrophic phases was 40, 11, 10, 0 and 20, respectively. The rate of agreement with those using LBP was 87.7%. (2) Incidences of large clusters, ductal clusters, palisade arrangement, uneven staining and dirty mucous background detected were significantly higher with the conventional method, whereas with LBP clean background, inconspicuous bonding of cells, scattered solitary glandular cells, clear well-stained cytoplasm and cell compactness were higher. (3) Especially in the proliferative phase, clusters tended to be smaller and lose their architectural structures, and scattered solitary columnar cells were present. (4) Cells in the mid-phase tended to have loose contact and to mimic other phases. Conclusions: Cytodiagnosis of endometrial phasing prepared with LBP is feasible to perform when some modifications are implemented.

Background: The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium. Methods Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry. Results: The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase. Conclusions: Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2 (TIMP-2) expression immunohistochemically in endometriotic tissues and normal endometrium, our retrospective study considered 194 patients affected by endometriosis and 71 patients with normal endometrium. Tissue microarrays were created from paraffin-embedded blocks; immunohistochemistry was used to assess protein expression. In endometriotic tissues, survivin was expressed at a higher level than in normal endometrium; its glandular expression level was higher in non-ovarian than in ovarian endometriotic tissues and lower in stromal components. Endometrial tissues from women without endometriosis and endometriotic tissues had different matrix metalloproteinase expression profiles. MMP-2 and MT1-MMP correlated with TIMP-2 in endometriotic tissues. Furthermore, in endometriotic tissues, expression of survivin, aurora B kinase, and Ki-67 showed a significant positive correlation, which indicates a role in cellular proliferation that could be closely linked to its anti-apoptotic activity in endometriosis development. Our results imply a role for matrix metalloproteinases in endometriosis invasiveness; correlation of their expression with that of TIMP-2 underscores its possible key regulatory role.

Objective: It was the aim of this study to evaluate the diagnostic utility of Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology. Study Design: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were subjected to immunocytochemical staining for Notch-1, and we examined the labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells to total cells). We compared (1) the Notch-1 LI in normal endometrium, (2) the Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma. Results: In analysis item 1, the LI of Notch-1 was 32.9 ± 8.4, 19.4 ± 8.2 and 12.5 ± 7.5% in proliferative endometrium, secretory endometrium and atrophic endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial adenocarcinoma was 45.2 ± 7.4%, which was significantly higher than that in normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 ± 8.3%, which was significantly lower than that in endometrial adenocarcinoma. Conclusion: In conclusion, Notch-1 immunocytochemistry is a useful method for distinguishing between EGBD and endometrial carcinoma in endometrial cytology.

Objectives Endometrial resection is a procedure often performed for treatment of menorrhagia. Despite the fact that amenorrhoea frequently ensues, some normal endometrium can remain present and become the implantation site of a pregnancy. Such an event is uncommon (0.7%); however, the likelihood of an ectopic pregnancy is increased. This case report calls the reader's attention to the risk of intra- and extrauterine pregnancies and the necessity for contraception after endometrial resection, even in cases where amenorrhoea supervenes.Case A 46-year-old woman with prior endometrial resection and subsequent amenorrhoea, was diagnosed with a cornual pregnancy. She was successfully treated with systemic methotrexate, which was given in an outpatient clinic.Conclusion Clinicians should be aware of the increased likelihood of an ectopic pregnancy after endometrial resection. All women submitting to this procedure should be counselled about the need for contraception, even in cases where amenorrhoea deve...

To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one month after completion of RT. This case indicates that uterine adenomyosis in a premenopausal woman may show false positive uptake of (18)FDG-PET/CT associated with CCRT.

Objective: It was our aim to assess the usefulness of cytohistology in cervical thin layer brush samples with problems in the differential diagnosis of endometrial cells. Study Design: This study reveals the cytological, cytohistological and immunohistochemistry findings of 8 cases suspicious of adenocarcinoma in situ (AIS)/adenocarcinoma (AC) in cervical liquid-based cytology (LBC) preparations that turned out to be normal endometrial cells. Results: All 8 cervical LBCs featured endometrial and atypical endocervical-like columnar cells with frequent ragged ‘feathered’ edge appearance and rosette formations. Overlapping atypical glandular cell groups were present on 2 ThinPrep slides as well. In cytohistology of 7 cases, the recognition of endometrial stroma with endometrial glands easily allowed the diagnosis of normal endometrium. In 1 case with very small loose tissue fragments without glands, the diagnosis could be established by positivity for CD10 marker (endometrial stroma) and without proliferative activity in the Ki-67 immunostaining. Conclusion: In cervical LBC preparations, nuclear hyperchromasia, pleomorphism and nucleoli in normal endometrial cells are more obvious than in conventional smears, and their arrangement is sometimes suggestive of AIS or AC. In the 8 cases presented, we could avoid a false-positive diagnosis of AIS or AC through cytohistology/immunohistochemistry, and in consequence, unnecessary colposcopical/histological examination.

Human gene icb-1 (C1orf38) has been initially cloned by our group from endometrial adenocarcinoma cells. In this study, we examined icb-1 expression in 90 endometrial cancer and normal endometrial tissue specimens. Expression of icb-1 was significantly (about 3.5-fold) higher in endometrial cancer than in normal endometrium (p

Zusammenfassung 1. Von uber 200 wegen Pyometra oder chronisch-eitriger Endometritis hysterektomierten Hundinnen wurden 161 Uteri einschlieslich der zugehorigen Ovarien histologisch und pathologisch-anatomisch ausgewertet. 2. Nach den an diesem Material gewonnenen Erkenntnissen werden die entzundlichen Gebarmuttererkrankungen der Carnivoren mit ihren vielfaltigen Formvarianten unabhangig von ihrer klassischen pathologisch-anatomischen Einteilung in einen funktionell pathogenetischen Formenkreis eingeordnet, dessen Abhangigkeit vom Sexualcyclus dargestellt wird. Das Auftreten von Pyometrafallen, die nach morphologischen Merkmalen in spontaner Ruckbildung begriffen sind, ist der funktionell bestimmten Auffassung der “Typischen Pyometra” als Pseudograviditat analog. Die “Involutionsformen” der Pyometra unterscheiden sich nicht nur durch charakteristische Formabweichungen von den Typischen Pyometren, sondern auch durch die Funktionsphasen ihrer begleitenden Gelbkorper, die m. o. w. stark ruckgebildet sind. 3. Die Pyometrainvolution geht unter spontaner Entleerung des Inhalts, Volumenverminderung und Wiedererlangung der Kontraktionsbereitschaft der Muscularis vor sich. Histologisch finden sich Reparation von Epithelverlusten der Mucosa durch Epithelregenerate aus Drusenresten, Hyperplasien der Schleimhaut und der zirkularen Muscularisschicht. Die Pyometrainvolution endet in einer chronisch-eitrigen (hyperplastischen) Endometritis (scheinbare Spontanheilung der Pyometra). 4. Die Pyometren, deren Ruckbildung wegen tiefgreifender Zerstorung von Mucosa und Muscularis durch Entzundungsvorgange nicht moglich ist, werden als “persistierend” bezeichnet. 5. Besondere Beachtung verdienen Formen, die dadurch auffallen, das am scheinbar unveranderten Uterushorn unvermittelt im Sinne einer Typischen Pyometra veranderte, stark ausgeweitete Segmente auftreten. Sie werden mit den sog. Einhorn-Pyometren im Begriff der “partiellen Pyometren” zusammengefast. Die Ursache einer Pyometraentwicklung, die auf isolierte Hornsegmente beschrankt bleibt, ist noch zu klaren. 6. Bemerkenswert ist die Bildung ringformiger Hyperplasien der inneren Muscularisschicht in Form von Querfalten oder von Septen, die Pyometra-Ampullen hermetisch abriegeln konnen. Sie finden sich bei allen Formen des Pyometra-Endometritiskomplexes und sind nicht selten mit Wandphlegmonen, Abszesbildung der Wand und eitrigen Durchbruchen in die Bauchhohle verbunden. Die Muscularishyperplasien sind als Folge autonomer Reaktion einzelner Muscularissegmente zu betrachten. 7. Die Strukturmodifikationen des normalen Endometrium wahrend Graviditat und Puerperium werden mit histologischen Besonderheiten der Uterusmucosa von Pyometren und Endometritiden verglichen. Dabei werden Analogien der histologischen Bilder der normalen und der pathologisch veranderten Schleimhaut deutlich. Insbesondere konnen pseudodeciduale und pseudopuerperale Strukturen unterschieden werden. Diese sind als organspezifische Reaktionen der Uterusmucosa aufzufassen, die wahrend und nach der Luteinphase durch den Entzundungsreiz ausgelost werden. Summary Studies on the pathological histology, pathogenesis and aetiology of the pyometra-endometritis complex in the bitch 1. From a series of 200 bitches, hysterectomised because of pyometra or chronic purulent endometritis, a total of 161 uteri and ovaries were evaluated histologically and pathologically. 2. On the basis of this material the inflammatory changes in the uterus of carnivores are classified so as to show their relationship to the sexual cycle. Cases of pyometra which resolve spontaneously are designated ‘involution forms’. This term according with the interpretion of the so called ‘typical pyometra’ as a functional condition of pseudo pregnancy. The ‘involution forms’ of pyometra differ from the typial form not only in respect of the uterine changes but also by the corpus luteum having markedly regressed. 3. Involution of pyometra occurs by spontaneous emptying of the contents, reduction in volume and re-emergence of the contractile ability of the musculature. Histologically, the epithelium which had been lost is repaired by regeneration from glandular remains, and hyperplasia of the mucosa and the circular muscle. The involution ends in a chronic purulent (hyperplastic) endometritis (apparent spontaneous cure of pyometra). 4. Cases of pyometra in which regression is not possible because of depth of the damage to the mucosa and musculature by inflammatory changes are designated ‘persistent’. 5. Special attention is given to cases characterised by markedly widened segments of the uterine horns in an otherwise apparently normal uterus. These are grouped together under the term ‘partial pyometra’. The reason for localisation of the condition to segments of the horns is so far unexplained. 6. Noteworthy is the formation of ring-like hyperplasia of the inner muscle in the form of transverse folds or septa which can hermetically seal the pyometra ampullae. These occur in all forms of the pyometra-endometritis complex and are not infrequently associated with diphtheritic and purulent changes in the wall and rupture into the peritoneal cavity. The muscular hyperplasia is interpreted as the result of autonomous reactions of individual muscle segments. 7. The structural changes of the normal endometrium during pregnancy and the puerperium are compared with those in pyometra and endometritis. In this way analogies between the histological appearance of the normal and diseased mucosa can be seen clearly and, in particular, pseudo-decidual and pseudo-puerperal structures can be distinguished. These are seen as specific reactions of the uterine mucosa which are brought about during and after the luteinising phase by the inflammatory stimulus. Resume Recherches sur l'histopathologie, la pathogenie et l'etiologie du complexe endometrite-pyometrie de la chienne I. L'anatomie clinique et l'histopathologie de la pyometrie 1. Sur un total de plus de 200 chiennes ayant subi une hysterectomie pour cause de pyometrie ou d'endometrite chronique purulente, 161 uterus et les ovaires correspondants ont fait l'objet d'une etude anatomo-pathologique et histologique. Selon les elements qui ont pu etre recueillis grâce a ce materiel, les lesions inflammatoires de la matrice des carnivores et leurs variantes morphologiques multiples peuvent etre rassemblees dans un groupe fonctionnel et pathogenique uniforme independemment des distinctions anatomo-pathologiques classiques. Elles forment le complexe endometrite-pyometrie qui est en rapport avec le cycle sexuel. Les formes dites d'involution comprennent les pyometries qui d'apres leurs caracteres morphologiques presentent une involution spontanee. Elles se distinguent des pyometries typiques par des differences anatomiques caracteristiques et par le degre d'involution du corps jaune. 2. Dans le cadre des analyses histologiques les lesions de l'endometrium des ampoules isolees existant dans les “pyometries partielles” furent etudiees specialement ainsi que le comportement de la couche musculaire de la paroi dans la formation des segments et des cloisons. L'analogie de certaines lesions de la muqueuse dans certaines formes de pyometries avec les modifications de structure de l'endometrium normal pendant la gravidite et le puerperium permettent de conclure a des formations dodeciduales et puerperales. Elles doivent etre considerees comme des reactions specifiques de la muqueuse uterine qui sont provoquees pendant et apres la phase de luteinisation des ovaires par des excitations non specifiques. Resumen Estudios sobre la histopatologia, patogenia y etiologia del complejo piometra-endometritis de la perra I. La anatomia clinica e histopatologia de la piometra 1. De entre mas de 200 perras histerectomizadas debido a piometras o endometritis cronico-purulentas, se valoraron 161 uteros con sus respectivos ovarios histologica y anatomopatologicamente. Segun los conocimientos adquiridos con este material, se encuadran las metritis de los carnivoros con sus multiples variantes de forma, independientemente de su clasificacion anatomopatologica, en un circulo formal funcionalmente patogenico (complejo piometra-endometritis), exponiendose su dependencia del ciclo sexual. En el concepto “formas involutivas” se reunen aquellas piometras, que segun las caracteristicas morfologicas estan comprendidas en la regresion espontanea. Se diferencian de las piometras tipicas por desviaciones caracteristicas de forma y en el grado de regresion de sus cuerpos amarillos concomitantes. 2. En el marco de los analisis histologicos se evaluan muy en especial las alteraciones endometricas de las ampollas de piometra, de presentacion aislada, de piometras “parciales” y el comportamiento de la capa muscular de la pared uterina en la formacion de segmentos y septos. Analogias de las alteraciones de la mucosa de determinadas formas de piometra con las modificaciones estructurales del endometrio normal durante la gravidez y el puerperio permiten colegir formaciones pseudodeciduales y pseudopuerperales. Se deben admitir como reacciones especificas de organo de la mucosa uterina, que son desencadenadas durante y despues de la fase luteinica de los ovarios mediante estimulos inespecificos.

The endometrium is greatly affected by sex-steroid hormones. It is immature in childhood, shows histological alteration depending on menstrual cycle, and becomes atrophic after menopause. Inflammation, dysfunctional bleeding and endometrial polyps are representative non-neoplastic lesions. The latter two lesions should be differentiated from endometrial hyperplasia or carcinoma, considering various metaplastic lesions and artifacts, especially in biopsy specimens. Endometrial hyperplasia has a pre-cancerous nature, and is classified into simple, complex, simple atypical and complex atypical hyperplasia. Complex atypical hyperplasia develops into carcinoma at a high frequency. Differentiation of atypical hyperplasia from well-differentiated adenocarcinoma is often difficult in small biopsy specimens. Endometrial carcinoma includes endometrioid adenocarcinoma, serous adenocarcinoma, clear cell adenocarcinoma, mucinous adenocarcinoma, squamous cell carcinoma and undifferentiated carcinoma. Endometrioid adenocarcinoma is most common and sub-classified into Grade 1 to 3, depending on atypia. There are tumors consisting of epithelial and mesenchymal components: adenofibroma, adenosarcoma, carcinofibroma and carcinosarcoma. Immunohistochemistry is sometimes required to confirm characteristics of the components. During pregnancy, the placenta changes histologically with the development of a fetus. Cytotrophoblasts and syncytiotrophoblasts are observed in chorionic villi, and intermediate trophoblasts in the area of implantation. Trophoblastic diseases include hydatidiform moles, choriocarcinoma, placental-site trophoblastic tumors and persistent trophoblastic disease. Chorionic villi swell more than 2 mm in diameter with cistern formation in hydatidiform moles, which are sub-classified into complete and partial moles. Choriocarcinoma is pregnancy-related or non-pregnancy-related. Atypical trophoblasts proliferate with severe hemorrhage and necrosis.

The purpose of the current study was to examine the use of thin-layer cytologic (TLC) preparation compared to conventional cytologic preparation (CCP) in the normal endometrium (proliferative, secretory, atrophic) and endometrial glandular and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by collecting a direct endometrial sample using the Uterobrush. The material comprised 40 cases of proliferative endometrium, 42 cases of secretory endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The following points were investigated: (1) number of endometrial epithelial cell clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3) number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on number of condensed cluster of stromal cells; (5) presence of metaplastic clumps with irregular protrusion-containing condensed stromal cluster; (6) presence of a clear background; (7) presence of blood vessel in TLC; (8) presence of blood vessel of length more than diameter of a field in object x20 glasses in TLC. (1) In all phases, the number of epithelial cell clumps per a unit area of a preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of stromal cells and metaplastic clumps with irregular protrusion-containing condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on the appearance of a clear background. (4) The proliferative endometrium and secretory endometrium were highly significant in comparison with atrophic endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel of length more than diameter of a field in object x20 glasses. Although the preparation area of TLC is smaller than that of CCP, the preparation has a clean background so that an accurate report on the patient's condition is possible. Therefore, TLC preparation is a useful tool for the accurate and reliable diagnosis of normal endometrial phase and EGBD, because the preparation area is confined and identification of the target cell clumps is easy.

To investigate changes in tight junctions between microvascular endothelial cells in normal endometrium.A quantitative transmission electron microscopy study of changes in the number of tight junctions per microvessel, and widths and lengths of individual junctions at different phases of the menstrual cycle.Two types of tight junctions were defined ("open" and "closed") which varied in the degree of separation between apposed plasma membranes of endometrial endothelial cells. Tight junction density was greater in proliferative than secretory phases (p0.02). The width and length measurements of individual tight junctions changed during menstruation.The two types of tight junctional contacts and the changes in width and density may reflect variation in structure and function between adjacent endothelial cells. These junctions may have importance in the processes of implantation and menstruation.

Objective: To explore the role of matrix metalloproteinase-1, 2 (MMP-1, MMP-2) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in endometriosis. Methods: The eutopic and ectopic endometria from 40 subjects suffering from endometriosis and regular. endometria from 40 subjects (excluding endometriosis) were collected and examined by in situ hybridization technology and western blot assay. Results: Both expressions of MMP-1 and -2 were stronger in ectopic endometrium and eutopic endometrium than in normal endometrium. On the contrary, the expression of TIMP-1 in ectopic endometrium and eutopic endometrium was lower. The differences were significant (P＜0.01). Moreover, there was no relationship, among the expressions of MMP-1, 2 and TIMP-1 in ectopic endometrium. Conclusion: The expressions of MMP-1, 2 and TIMP-1 lose balance and lack of periodic changes in ectopic endometrium, which explains the biological invasive behavior of endometriosis. It was suggested that regulating the balance between the MMPs and TIMP-1 should be an ideal therapeutic target to endometriosis.

Intrauterine adhesions are a result of trauma to the gravid or non-gravid uterus. Such trauma might derive from curettage of uterus, various forms of hysteroscopic surgery, Caesarean sections, uterine artery embolisation (UAE) and uterine devascularisation. Following the trauma to the uterus, endometrial fibrosis, adhesion bands and obliteration of uterine cavities may follow. Normal endometrium has two distinctive layers: functional layer and basal layer. Damage to the functional layer is often followed by regeneration of a new functional layer from a healthy basal layer. However, damage to the basal layer might disrupt the process of endometrial regeneration and promote the formation of fibrosed tissue. Hysteroscopic adhesiolysis is an effective method of treatment for intrauterine adhesions. However the procedure is often complicated by recurrence of adhesions. Therefore, effective methods are necessary to prevent reformation of intrauterine adhesions.

Summary Nucleolar organizer regions (NORs) were evaluated in 11 women with adenomyosis. The material, sampled during operations, was silver-stained using the technique of Ploton et al. and verified histopathologically. A hundred cell nuclei per slide were assessed. The examined variables comprised the number of argyrophylic nucleolar organizer regions (AgNORs) in the nucleus, the surface area of a single AgNOR and the position of the AgNORs in the cell nucleus, as well as the AgNORs’ coefficient, which were all estimated under a microscope. The parameters were quantitatively assessed using computer image analysis software Multi-Scan Base V.8. Adenomyosis was found to be associated with a significant decrease (up to 60%) in the nuclear area, as well as with a marked reduction (up to 50% as compared with normal endometrium) in the number of AgNOR granules. The total area of AgNORs in the cell nucleus also decreased from 3.55 to 1.57 μm2. There were no significant differences in the number of granules per nucleus either in the control group or in the adenomyosis group. The AgNOR coefficient was found to be lower in adenomyosis compared to normal endometrium.

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P = .012 and P = .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P = .0003) and high FIGO grade (P = .004) and with cancers showing either deep myometrial invasion (P = .023), lymph node metastasis (P = .006), lymphvascular space involvement (P = .048), or positive peritoneal cytology (P = .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P = .004 and P = .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.

Objective: To investigate the expression of PTEN in endometrial carcinoma and its clinical significance. Methods: Reverse transcriptase-polymerase chain reaction and Western-blot methods were used to detect PTEN expression in 28 cases of endometrial carcinoma. Results: mRNA and protein expression levels of PTEN in endometrial carcinomas were significantly lower than those in normal endometrium (P

We compared ultrasound images of the uterine cavity obtained by sonohysterography (SHG) with those of hysteroscopy in an attempt to avoid inaccurate interpretations. Women referred for abnormal bleeding or infertility underwent SHG before treatment. Those with an abnormal study underwent hysteroscopy for confirmation and treatment. Abnormal SHG studies are frequent, with false positive images including blood clots, mucus plugs, and shearing of normal endometrium relatively common. Uterine pathology generally seen on SHG, including anomalies, polyps, and myomas, is consistent with that seen at hysteroscopy. Performing intraoperative SHG concomitantly with hysteroscopy adds value due to SHG's three-dimensional images to confirm depth of pathology and false negative hysteroscopy findings.

Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, that is, deficient 17beta-HSD type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.

Although described for the first time some decades ago, the contribution of the immune system to the establishment of tumors has not been extensively pursued for a long time. Over the last decade, however, more and more evidence has been accumulating concerning the role the immune system plays in tumor development and progression and its possible role in patient prognosis. In addition, interest is growing in preclinical and clinical research concerning the use of the immune system in the treatment of cancer. Immunotherapy for gynecological cancers in general, and for endometrial cancer in particular, is still in its infancy. Only a small number of studies, with varying success rates, have been published. Here, we provide a concise overview of the literature available on the role of the immune system in the normal endometrium and in endometrial cancer, in addition to the possible implications for future immunotherapeutic studies. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Endometriosis is an inflammatory, estrogen-dependent disease characterized by the growth of endometrial tissues outside the uterus. The eutopic endometrium from women with endometriosis has some fundamental differences compared with the normal endometrium of women without endometriosis. The differences could contribute to the survival of regurgitating endometrial cells into the peritoneal cavity and the development of endometriosis. One mechanism that gained a lot of interests is the finding that apoptosis appeared in eutopic and ectopic endometrium of patients with endometriosis. A common characteristic of endometriotic cells is their ability to evade the apoptotic machinery. Endometriosis could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. This chapter focused on the physiological role of apoptosis in normal endometrium and the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Finally, the role of apoptosis in the treatment of endometriosis is reviewed to link the basic research findings into clinical applications.

Potential activity of Ca2+/Mg2+-dependent endonuclease in hyperplastic endometrial tissues is lower than in normal endometrium and practically absent in endometrial cancer tissue. Thus, molecular mechanisms of apoptosis regulation are disturbed even at the stage of hyperplasia.

Background: To develop a supplementary diagnostic method for endometrial cancer by measuring the reactivity of various endometrial lesions with two monoclonal antibodies. Methods: We investigated the reactivity of various endometrial lesions with two monoclonal antibodies (MSN-1 and MSN-3) by flow cytometry (one-color and two-color methods). Results: The two-color method appeared to be suitable for use in place of simultaneous performance of the one-color methods with MSN-1 and MSN-3. The positivity rate for normal endometrium was 16.0% with the two-color method, which was lower than the rate of 30.0% obtained with concomitant used of the one-color methods. The positivity rate for endometrial cancer was high, 84.0%, with the two-color method. The positivity rate was 85.7% for well-differentiated endometrial cancer, 71.4% for moderately differentiated cancer, and 100.0% for poorly differentiated cancer; thus, the rate was high irrespective of the cellular differentiation. Conclusions: The two-color method is more useful than the one-color method as a supplementary diagnostic procedure for endometrial cancer. Cytometry 36:150–156, 1999. © 1999 Wiley-Liss, Inc.

Objective. To investigate the relationship between body mass index (BMI) and transvaginal ultrasonographic endometrial thickness. Materials and methods. Two hundred and twelve postmenopausal Japanese women (mean age, 62.1±8.0 years; range 47-85) with histologically proven normal endometrium and with endometrial thickness more than 1.0 mm were studied. Baseline characteristics including age. years since menopause, and BMI were recorded for each subject. The relationship between sonographic endometrial thickness and baseline characteristics was assessed in each subject. Results. BMI was significantly correlated with endometrial thickness (r=0.40, p

Objective: To clarify the behavior of endometrial hyperplasia in a prospective study. Method: Fifty-one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow-up. Results:/ In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow-up, after showing a normal endometrium. Conclusion: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.

Glands are lined by a single layer of flattened or cuboidal epithelial cells containing bland nuclei without mitoses. Mucus is scant. Glands may be fragmented.

Background Diffusion-weighted magnetic resonance imaging (DWI) is increasingly used in the diagnosis of endometrial disease. No complete knowledge, however, exists yet of the influence of physiology on the endometrial apparent diffusion coefficient (ADC) values on which DWI is based. Purpose To establish whether the ADC values measured with DWI in the endometrium of healthy reproductive-aged women significantly vary from the early proliferative to the periovulatory phase of the menstrual cycle and between the fundus and the isthmus of the uterus. Material and Methods In 17 women the endometrial ADC values measured on the fifth menstrual day, both at the fundus and at the isthmus of the uterus, were compared to the values obtained on the 14th day before the subsequent cycle. In 81 women (menstrual day: fifth through 21st) the endometrial ADC values measured at the fundus were compared to the values obtained at the isthmus of the uterus. All examinations were performed with a 1.5 T magnet (b values: 0 and 800 mm/s2). The results were analyzed by means of Student's t-test per paired data. Results The endometrial ADC values measured on the fifth day of the menstrual cycle were lower than those obtained in the periovulatory phase both at the fundus (mean 0.923 vs. 1.256 × 10−3 mm2/s) and at the isthmus (mean 1.297 vs. 1.529 × 10−3 mm2/s) of the uterus. The endometrial ADC values measured at the fundus of the uterus were lower than those obtained at the isthmus (mean 1.132 vs. 1.420 × 10−3 mm2/s) through the menstrual cycle. All these differences were highly significant ( P < 0.001) at statistical analysis. Conclusion Physiological variations occurring in endometrial ADC values of healthy women should be considered by the radiologists when interpreting DWI examinations in patients with endometrial disease.