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[Treatment of benign uterine hemorrhage and simple endometrial hyperplasia by endometrial ablation].

BACKGROUND AND AIMS: The technique of endometrial resection by resectoscope represents a valid alternative to hysterectomy in patients with a high operating risk suffering from benign uterine bleeding and simple endometrial hyperplasia refractory to medical treatment or uterine curettage. The aim of this study was to demonstrate the validity of the resectoscopic technique of endometrial ablation. METHODS: The authors performed endometrial ablation using a loop and roller resectoscope in a group of 24 women with refractory menorrhagia which failed to respond to other techniques of first choice. RESULTS AND CONCLUSIONS: The results obtained show the good tolerability of resectoscopic surgery by the patients who, for medical reasons, represented a high operating risk if subject to laparohysterectomy.

Adult↗
PubMed1997

The behavior of endometrial hyperplasia: a prospective study. Endometrial Hyperplasia Study Group.

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.

Adult↗
PubMed1996

[The relationship between simple and atypical endometrial hyperplasia and endometrial carcinoma].

The study was carried on 101 women in the perimenopause and postmenopause. The patients were divided into three groups, according to the results of the pathomorphological examination: I group--patients with simple hyperplasia; II group--patients with atypical hyperplasia; III group--patients with endometrial carcinoma. The simple hyperplasia predominates in the perimenopause, while the endometrial carcinoma was the most frequent cause for metrorrhagia in the postmenopausal women. When the endometrial carcinoma was combined with hyperplasia there were higher differentiation and less invasiveness of the endometrial carcinoma in these cases.

Adult↗
PubMed2003

Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer.

BACKGROUND: Successful treatment of endometrial hyperplasia with progestins is commonly accompanied by the finding of an inactive or suppressed endometrium after therapy. However, approximately 30% of the endometrial hyperplasia cases do not respond to progestins and hyperplastic glands persist. The Fas/FasL system is known to play a role in tissue remodeling as a result of changes in menstrual hormone levels. The aims of this study are to examine Fas/FasL expression in endometrial hyperplasia of pre- and postprogestin treatment samples and to study the Fas/FasL regulation in vitro with Ishikawa cells after progestin stimulation. DESIGN: Pre- and posttreatment paraffin-embedded endometrial hyperplasia tissue samples from 26 women were examined by immunohistochemistry for changes in Fas/FasL expression related to the administration of progestins. Among 26 patients, 18 were successfully treated with progestins and 8 failed treatment. Fas/ FasL positivity was defined by the presence of 10% or more immunoreactive epithelial cells in each specimen. In positive cases, a percentage or an immunoscore of immunoreactive cells was given by counting 500 cells. Cell viability was evaluated by the MTT assay. The in vitro effects of progesterone on Fas/FasL expression and apoptosis in Ishikawa cells were examined by using Western blot and TUNEL assays, respectively. RESULTS: Fas immunoreactivity was present in 4/26 (15%) preprogestin cases with an average of 16% of the epithelial cells expressing Fas. FasL was expressed in 21/26 (80%) pretreatment cases with an average of 42% of the hyperplastic glandular cells being positive. In postprogestin cases, an increase of Fas expression (14/18, 77%) with an average of 47% stained cells was seen in responders (P < 0.001), while FasL was found in 16/18 (89%) responders with an average of 65% of cells positive (P = 0.587). In nonresponders, no significant changes in Fas/FasL expression were detected compared to pretreatment samples. With in vitro Ishikawa cells, a slight increase (10-20%) of Fas and FasL protein expression was detected after 24 h of progesterone treatment, but a more significant increase (220-343%) of both Fas and FasL expression was found after 48 h of withdrawing progesterone, which parallels apoptotic activity. CONCLUSIONS: The Fas/FasL system may be involved in the development of endometrial hyperplasia. Part of the molecular mechanisms of progestin therapy for endometrial hyperplasia is through upregulation of Fas/FasL expression. Dysregulation of Fas/FasL expression in hyperplastic endometrium may be part of the molecular mechanisms for nonresponders to progestin treatment. Intermittent, rather than continuous, progestin treatment may be more effective clinically for the treatment of endometrial hyperplasia.

Adult↗
PubMed2006

GLUT-1 is preferentially expressed in atypical endometrial hyperplasia and endometrial adenocarcinoma.

The facilitative transport of monosaccharides in human cells is accomplished by a family of transmembrane proteins, GLUT-1 to GLUT-7, that differ in their tissue distribution, affinities for specific monosaccharides, and physiologic regulation. GLUT-1, a high-affinity glucose transporter, is normally expressed in erythrocytes, the perineurium of peripheral nerves, and capillary endothelial cells of the blood-brain barrier. Although the aberrant expression of GLUT-1 has been reported in a wide spectrum of epithelial malignancies, its possible correlation with the malignant transformation of endometrial epithelium has not been clearly established. The purpose of this study was to evaluate the extent to which benign, hyperplastic, atypical, and malignant endometrial epithelia express GLUT-1. The authors examined the IHC expression of GLUT-1 in cases of proliferative endometrium (n=12), secretory endometrium (n=10), endometrial polyps (n=10), adenomyosis (n=18), simple hyperplasia (n=14), complex hyperplasia without atypia (n=17), complex hyperplasia with atypia (n=17), and adenocarcinoma (n=31). Positive staining was defined as distinct, linear membrane staining, particularly at cell-cell borders. Cells that showed only cytoplasmic staining were considered negative. The percentages of positive cells and staining intensity were assessed in a semiquantitative fashion and scored (1+ to 3+). All cases from proliferative endometrium, secretory endometrium, adenomyosis, and simple hyperplasia and 90% (9/10 cases) of the endometrial polyps were negative for GLUT-1. GLUT-1 was expressed in 24% (4/17 cases) of complex hyperplasia without atypia, 71% (12/17 cases) of complex hyperplasia with atypia, and 90% (28/31 cases) of adenocarcinomas. The extent of staining ranged from occasional positive foci to extensive multifocal staining. GLUT-1 positivity increased in intensity as the distance of tumor cells to stroma increased. The authors conclude that GLUT-1 is preferentially expressed in complex hyperplasia with atypia and in adenocarcinoma and that GLUT-1 immunostaining is useful in distinguishing benign hyperplasia from hyperplasia strongly associated with malignancy. GLUT-1-mediated glucose transport may allow hypoxic tumor cells distant from stromal blood vessels to survive through glycolysis. These data suggest that the expression of GLUT-1 transporter may be closely related to the malignant transformation of epithelial endometrial tumors by supporting their increased need for glucose metabolism.

Adenocarcinoma↗
PubMed2004

Diffuse cystic endometrial hyperplasia and metastatic endometrial adenocarcinoma in a vietnamese pot-bellied pig (Sus scrofa).

A 16-year-old female Vietnamese pot-bellied pig was euthanized after a period of inappetence and weight loss. Diffuse cystic endometrial hyperplasia and endometrial adenocarcinoma with metastasis to lymph nodes, liver, and lung were diagnosed. This report follows the recent description of cystic endometrial hyperplasia and uterine leiomyomas in 3 aged female Vietnamese pot-bellied pigs. The findings in this report and previous reports suggest that pigs may develop some similar age-related uterine lesions as do women.

Adenocarcinoma↗
PubMed1996

Endometrial hyperplasia and endometrial cancer.

Endometrial cancer is the most frequently seen gynecologic neoplasm, but it fortunately has low mortality, which is due largely to its presentation with abnormal bleeding and its subsequent early diagnosis. The morbidity associated with therapy for early lesions is moderate. Hyperplasia with atypia should be treated as early cancers. Many molecular markers are currently under study. Markers may soon help us identify invasive lesions at higher risk of recurring and thus more suitable for adjunct therapy. Screening in the general population is not recommended, but a high-risk group that is more suitable for screening could be identified, including obese and nulliparous women, those treated with unopposed estrogen or tamoxifen, or those with family or past histories of breast or colon cancer. Development of chemoprevention with an oral contraceptive during the reproductive years is under way, and there may be a role for chemoprevention in the reversal of hyperplasias.

Biomarkers, Tumor↗
PubMed2004

Gain of OGP, an estrogen-regulated oviduct-specific glycoprotein, is associated with the development of endometrial hyperplasia and endometrial cancer.

PURPOSE: Lesions in the endometrium are difficult to differentially diagnose. The present study examined whether oviduct-specific glycoprotein is differentially expressed in normal, hyperplastic, and malignant endometrium. EXPERIMENTAL DESIGN: The expression of oviduct-specific glycoprotein was characterized by immunohistochemical methods with whole sections of endometrium from 90 women. An endometrial cancer tissue microarray with 200 cases of endometrial cancer was also assessed for oviduct-specific glycoprotein, estrogen receptor, and PTEN expression. RESULTS: In normal endometrium, there was focal oviduct-specific glycoprotein expression in the basalis layer, where the stem cells reside, in 10 of 15 cases. On average, atypical hyperplastic endometria stained more intensely than hyperplastic endometria (P = 0.017), whereas the percentage of positively stained cells was not significantly different. The mean staining indices (intensity x percentage of positive cells score) for hyperplasia and atypical hyperplastic were 4.7 and 5.5 and were significantly higher than staining indices seen in normal cycling endometria or well-differentiated endometrioid endometrial carcinomas (P < 0.0001 and P < 0.001, respectively). The endometrial cancer tissue microarray showed that of 139 endometrioid endometrial carcinomas, 11 cases were strongly oviduct-specific glycoprotein positive, whereas the other 128 cases were negative or weakly positive. Analysis of Kaplan-Meier curves with log-rank statistics showed a trend toward significance, with strong oviduct-specific glycoprotein staining serving as a predictor of good prognosis (P = 0.1). There was a significant positive correlation between oviduct-specific glycoprotein staining and loss of PTEN in the cases of endometrial cancer (P = 0.004). CONCLUSIONS: Oviduct-specific glycoprotein may be a useful diagnostic adjunct to more accurately classify premalignant and early malignant change in the endometrium, improving on the current irreproducible histologic classification system.

Adenocarcinoma↗
PubMed1994

[Proliferative activity of normal endometrial cells, endometrial hyperplasia cells and endometrial cancer cells using the monoclonal antibody to PCNA].

PCNA (Proliferating Cell Nuclear Antigen) index was studied by using an immunohistochemical technique in normal endometrium (n = 44), endometrial hyperplasia tissue (n = 12) and endometrial carcinoma (n = 60). In normal endometrial tissues, the PCNA index in the late proliferative phase (n = 11, 26.8 +/- 2.7% (mean +/- SE)) was the highest, and showed a significantly higher value than those of the early-mid secretory phase (n = 7, 12.5 +/- 3.4%, p < 0.01), late secretory phase (n = 11, 0.2 +/- 0.1%, p < 0.001), early proliferative phase (n = 7, 6.4 +/- 2.9%, p < 0.001) and postmenopausal endometrium (n = 8, p < 0.001). The mean PCNA index of premenopausal endometrial carcinoma (n = 17) was 17.1% and was not significantly higher than those of the proliferative phase and endometrial hyperplasia. Postmenopausal endometrial carcinoma (n = 43) presented a mean PCNA index of 19.9%, which was significantly higher than that of normal postmenopausal endometrium (p < 0.005). There was a clear relationship between the PCNA index and nuclear grade, cervical involvement, muscle invasion, lymph-vascular space involvement and lymphnode metastasis, respectively. There was a statistically significant difference in survival between a PCNA index of less than 25% and a PCNA index of 25% or above (p < 0.05). These results suggest that PCNA immunoreactivity in endometrial carcinoma cells may be clinically useful in predicting and/or determining the prognosis, and/or the necessity of adjuvant therapy.

Adult↗
PubMed2003

Clinical over- and under-estimation in patients who underwent hysterectomy for atypical endometrial hyperplasia diagnosed by endometrial biopsy: the predictive value of clinical parameters and diagnostic imaging.

OBJECTIVE: The aim of this study was to analyze the clinical and imaging characteristics in patients diagnosed with atypical endometrial hyperplasia based on endometrial biopsy in comparison with the final diagnosis from resected uteri; i.e. to determine the rates of underestimation (endometrial cancer), equivalent diagnosis (atypical hyperplasia), and overestimation (hyperplasia without atypia or non-hyperplastic lesion). MATERIALS AND METHODS: We reviewed 33 patients who were diagnosed with atypical endometrial hyperplasia by endometrial biopsy using a small curette and then underwent total abdominal hysterectomy between September 1992 and May 2002. Clinical parameters obtained from patients' charts, and imaging analyses using transvaginal ultrasonography (TUS) and magnetic resonance (MR) imaging were retrospectively re-examined. RESULTS: Among 33 patients who underwent hysterectomy due to a diagnosis of atypical hyperplasia, nine cases (27.2%) were underestimated (cancer), nine cases (27.2%) were equivalent and 15 cases (45.6%) were overestimated as indicated by examination of the endometrium of the resected uterus. There was no difference among these groups in either clinical parameters or diagnostic images obtained by TUS or MR. CONCLUSION: Diagnosis of atypical endometrial hyperplasia by endometrial biopsy often resulted in under- or over-estimation, as shown by examination after hysterectomy. As there is neither a reliable clinical parameter nor imaging feature to distinguish between these groups, hysterectomy is still the best treatment for these patients if they are willing to give up their fertility.

Adult↗
PubMed1989

A comparative morphometric and cytophotometric study of endometrial hyperplasia, atypical hyperplasia, and endometrial carcinoma.

The DNA content and nuclear measurements of five groups of endometrial proliferations--proliferative endometrium (PE), simple hyperplasia (SH), atypical hyperplasia (AH), well-differentiated carcinoma (WDC), and poorly differentiated carcinoma (PDC)--were compared using 14 descriptors in a stepwise discriminant analysis. Classification using the discriminant rules agreed with the pathologic interpretation for 78% of the specimens. All PEs were assigned to the correct group, and 97% of benign endometria and carcinomas were correctly classified as benign or malignant. Only two of 39 hyperplasias (5%) were misclassified as malignant, and only one of 36 carcinomas was classified as benign. In the difficult distinction between AH and WDC, using all descriptors for the five groups, only 68% of the AH and 60% of the WDC classifications were in agreement with the pathologist of record. However, when discriminant rules addressing only AH and WDC were used, 37 of 39 AHs and WDCs were in concordance. This suggests that a morphometric distinction between AH and WDC is feasible.

Carcinoma↗
PubMed2003

Activation of the receptor protein tyrosine kinase EphB4 in endometrial hyperplasia and endometrial carcinoma.

BACKGROUND: Members of the Eph family of tyrosine kinases have been implicated in embryonic pattern formation and vascular development; however, little is known about their role in the adult organism. We have observed estrogen-dependent EphB4 expression in the normal breast suggesting its implication in the hormone-controlled homeostasis of this organ. Since the endometrium is a similarly hormone dependent organ and endometrial carcinoma is thought to result from estrogenic stimulation, we have investigated EphB4 expression in normal human endometrium and during its carcinogenesis. PATIENTS AND METHODS: EphB4 expression was analyzed immunohistochemically in 26 normal endometrium specimens, 15 hyperplasias and 102 endometrioid adenocarcinomas and correlated with clinical and prognostic tumor characteristics. RESULTS: In normal endometrial tissue no EphB4 protein was detected. Strikingly, we observed a drastic increase (P <0.0001) in the number of EphB4 protein-expressing glandular epithelial cells in the majority of hyperplasias and carcinomas. Moreover, we found a statistically highly significant positive correlation between EphB4 expression and post-menopausal stage of the patient (P = 0.007). CONCLUSIONS: These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic intervention.

Adult↗