[The pathogenetic relationships between atypical hyperplasia, endometrial carcinoma and the E2 and progesterone levels].
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Carcinoma↗
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Results for “ENDOMETRIAL HYPERPLASIA”
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[An immunohistochemical study of the steroid hormone receptors in endometrial hyperplasia].
AIM: Evaluation of the estrogen and progesterone receptors (ER and PR) in different degrees of endometrial hyperplasias. METHODS: 10 cases of each degree of endometrial hyperplasia (simple, complex and atypical) were analyzed using the avidin-biotin-peroxidase technique and monoclonal antibodies applied to formalin-fixed, paraffin-embedded tissue. RESULTS: We found similar, high level of both ER and PR in simple and complex hyperplasias and a significant decrease of these in atypical hyperplasia. CONCLUSIONS: Endometrial hyperplasias develop in a setting of estrogen excess. This explains the high level of endometrial receptors and the response to progesterone in typical hyperplasia. In atypical hyperplasia, the decrease of steroid receptors results in a low sensibility of this lesion to progestative therapy, but there are cases with high receptor levels which could have a chance for hormonal therapy.
Biomarkers↗
Incidence of endometrial carcinoma in patients with endometrial hyperplasia.
OBJECTIVE: The purpose of this retrospective study was to establish the risk of developing endometrial adenocarcinoma in patients diagnosed with endometrial hyperplasia. MATERIAL AND METHODS: The incidence of endometrial hyperplasia and its relation with endometrial adenocarcinoma was evaluated in 1,139 patients who presented with abnormal bleeding between January 2000 and December 2004; D&C was performed in all cases. There were 591 (51.88%) cases of simple endometrial hyperplasia, out of which 110 (18.61% from 51.88%) cases had atypia, 60 (5.26%) cases of complex hyperplasia, out of which 19 (31.66% from 5.26%) had atypia, and the remaining 488 (42.84%) had different forms of mixed hyperplasia. RESULTS: The incidence of endometrial adenocarcinoma was 3.87% in atypical hyperplasia and 0.81% in other forms, and was related only to cases with atypia in which the incidence was 0.61%. CONCLUSIONS: The most indicated measure to prevent endometrial carcinoma in cases with complex endometria hyperplasia with atypia is hysterectomy, while for other forms of hyperplasia, hormonal treatment is used but only under strict control.
Adenocarcinoma↗
Parameters of cellular immunity in perimenopausal patients with glandular and adenomatous endometrial hyperplasia.
No appreciable disorders of cellular immunity were detected in patients with glandular cystic endometrial hyperplasia. Atypical endometrial hyperplasia was associated with quantitative changes in T lymphocytes and their subpopulations, decreased level of lymphocytes carrying activation antigens, and increased count of natural killers. These changes can be characterized as immunocompensation.
Adult↗
DNA ploidy, cell cycle kinetics, and low versus high grade atypia in endometrial hyperplasia.
There have been few studies of DNA ploidy and cell cycle kinetics in endometrial hyperplasia. The authors studied archival cases of proliferative endometrium, simple, complex and atypical endometrial hyperplasia and well, moderately, and poorly differentiated endometrial adenocarcinoma by flow cytometry and also evaluated the significance of the degree of cytologic atypia (low versus high) in endometrial hyperplasia relative to the occurrence of carcinoma. All proliferative endometria, all types of hyperplasia and well and moderately differentiated carcinomas were diploid. Two-thirds of poorly differentiated adenocarcinomas were aneuploid. Neither S-phase fractions or proliferative fractions (S+G2M) could distinguish among the different types of hyperplasia or predict which hyperplasias were associated with carcinomas. The degree of cytologic atypia in atypical hyperplasia was not predictive of the occurrence of carcinoma. Poorly differentiated carcinomas showed significant differences in DNA ploidy, S-phase, and proliferative fractions from endometrial hyperplasia and lower grade carcinoma. These results support the concept that there are two fundamentally different types of endometrial carcinoma.
Adenocarcinoma↗
The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma.
Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.
17-Hydroxysteroid Dehydrogenases↗
Differential diagnosis between normal endometrium and endometrial hyperplasia with immunostaining cytology using anti-LeY monoclonal antibody.
We have previously reported that both endometrial cancer and endometrial hyperplasia stain positively for the anti-LeY monoclonal antibody, whereas normal endometrium does not. Endometrial hyperplasia is a premalignant change associated with the eventual development of endometrial carcinoma. However, it can be difficult to differentiate hyperplasia from normal endometrium in cytology. This study illustrates the use of immunocytochemical cytology using anti-LeY monoclonal antibody to differentiate between endometrial hyperplasia and normal endometrium. Immunostaining using anti-LeY monoclonal antibody was performed on cytologic specimens obtained from 17 normal endometria, 25 endometria with endometrial hyperplasia, and 13 endometria with endometrial carcinoma. All normal endometria displayed negative staining for anti-LeY monoclonal antibody, whereas all endometria with endometrial carcinoma displayed positive staining. Of the endometrial hyperplasia cases, 21 displayed positive staining. However, four displayed negative staining due to the small number of cells available for diagnosis. We believe that immunostaining cytology using anti-LeY monoclonal antibody is a useful method for differentiating between normal endometrium and endometrial hyperplasia.
Antibodies, Monoclonal↗
Ezrin, a membrane-cytoskeletal linking protein, is highly expressed in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma.
We previously demonstrated that ezrin transcription was required for in vitro invasion and was involved in the acquisition of metastatic potential in endometrial cancer cells. In order to determine the functional role of ezrin in endometrial cancer, we examined ezrin protein expression in 20 cancerous and 33 non-cancerous tissues by immunohistochemistry and Western blot analysis. The specimens included 20 uterine endometrioid adenocarcinomas (UEC), seven simple endometrial hyperplasias (sH), seven complex endometrial hyperplasias (cH), seven atypical endometrial hyperplasias (aH), and 12 samples of normal endometrium (NE). Tissues of primary (P) and metastatic (M) lesions of endometrial cancers were obtained from five patients. Ezrin was specifically expressed in UEC and its precursor lesions. Ezrin expression was significantly higher in aH (P<0.05) and UEC (P<0.001) compared with NE, sH, and cH. In addition, ezrin was significantly highly expressed in M compared with P (P<0.05). Ezrin expression was associated with neither clinical stage nor histopathologic grade of UEC. In immunohistochemistry, ezrin was localized in the membrane of metastasized cancer cells, although ezrin was mainly distributed in the cytoplasm of most cancer cells and some endometrial hyperplastic cells. On Western blot analysis, ezrin was also detected in both cytosolic and membrane fractions in aH and UEC, whereas ezrin was detected in only cytosolic fraction in sH and cH. These data suggest that expression and subcellular distribution of ezrin protein play an important role in development and progression of UEC.
Adult↗
The value of curettage in diagnosis of endometrial hyperplasia.
OBJECTIVES: The aim of this study was to assess the value of diagnosis of endometrial hyperplasia by curettage and to determine the results of proliferating cell nuclear antigen (PCNA) immunostaining in differentiating endometrial carcinoma from endometrial hyperplasia. METHODS: According to Kurman's criteria, we treated 150 patients with endometrial hyperplasia detected by curettage and compared retrospectively the diagnosis by curettage with that by hysterectomy. PCNA expression was examined using immunohistochemostaining on 60 patients with complex atypical hyperplasia detected by curettage. RESULTS: Simple hyperplasia was found by curettage in 53 patients, complex hyperplasia in 11, simple atypical hyperplasia in 26, and complex atypical hyperplasia in 60. All patients were rediagnosed after hysterectomy. As a result, 65 were found to have simple hyperplasia, 7 complex hyperplasia, 15 simple atypical hyperplasia, 29 complex atypical hyperplasia, and 34 endometrial carcinoma. The accuracy of histological diagnosis by curettage was 76.7-92.0% and was dependent on different types of hyperplasia. Simple atypical hyperplasia and complex atypical hyperplasia were more likely to coexist with endometrial carcinoma than both simple hyperplasia and complex hyperplasia (chi2 = 26.3, P < 0.001), and complex atypical hyperplasia was more likely to coexist with endometrial carcinoma than simple atypical hyperplasia (chi2 = 9.78, P < 0.005). In complex atypical hyperplasia patients, coexistence with endometrial carcinoma was more common after menopause than before menopause (chi2 = 3.93, P < 0.05). In complex atypical hyperplasia patients, the expression of PCNA in cases associated with endometrial carcinoma was higher or stronger than in cases associated without endometrial carcinoma (chi2 = 7.68, P < 0.01, or U = 252.00, P < 0.01). Conclusions. Curettage tends to be more highly accurate in diagnosing simple hyperplasia than complex atypical hyperplasia, which is often found by hysterectomy to be associated with endometrial carcinoma. The expression of PCNA may be helpful in differentiating complex atypical hyperplasia from endometrial carcinoma.
Adult↗
A model for the study of cystic endometrial hyperplasia in bitches.
The aims of this study were: (i) to establish a reliable model for the study of cystic endometrial hyperplasia in ovariectomized bitches; and (ii) to assess the roles of oestrogen and progesterone in the pathogenesis of irritant-induced cystic endometrial hyperplasia. Greyhound bitches (n = 15) were ovariectomized and divided into five groups (n = 3 per group). After 3-4 weeks, oestradiol benzoate (0.6-4.8 micrograms kg-1, i.m.) was administered twice a day for 12 days to the bitches in group 1, followed by progesterone (0.2-1.8 mg kg-1, i.m.) twice a day for 30-33 days. These dosages were chosen to mimic the plasma hormone concentrations of a normal oestrous cycle. A silk suture was inserted by laparotomy into the left uterine horn 12 days into the simulated dioestrus (determined by vaginal cytology) and necropsy was performed after a further 12 days. For groups 2-5, the silk suture was positioned at ovariectomy. After a further 3-4 weeks, these bitches were treated with progesterone (group 2: 1.8 mg kg-1 i.m. twice a day), oestradiol benzoate (group 3: 0.6-4.8 micrograms kg-1 i.m. twice a day), oestradiol benzoate and progesterone together (group 4: previous dosages) or vehicle (group 5). Necropsies were performed after 12-13 days of treatment. Cystic endometrial hyperplasia was induced in the suture-containing uterine horns of all bitches in groups 1 and 4, and in two bitches in group 2. Cystic endometrial hyperplasia did not develop in any control (no suture) uterine horns, or in either uterine horn of the bitches treated with either oestradiol only or vehicle. These results indicate that progesterone is necessary for the development of irritant-induced cystic endometrial hyperplasia and that oestradiol potentiates the effects of progesterone. The protocol used for bitches in group 1 would be a suitable model for further studies of the pathogenesis of cystic endometrial hyperplasia.
Animals↗
The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia.
Forty eight patients in postmenopause affected by histologically confirmed endometrial hyperplasia (34 with simplex and 14 with complex forms) were administered Danazol therapy, 400 mg/day for 3 consecutive months. At the end of treatment, regression of the endometrial hyperplasia was histologically ascertained in 46 patients (95.9%) with disappearance of the metrorrhagia. Endometrial atrophy was obtained in 75% of the cases, while secretive (14.7%) or proliferative (6.2%) aspects resulted in the others. Only 2 patients (4.1%) showed persistence of the hyperplastic endometrium. On the basis of this experience, treatment with Danazol appears to be effective and safe with only scarce and transient side effects. This therapy is therefore proposed as a valid alternative to progestogen therapy in cases of postmenopausal endometrial hyperplasia.
Aged↗
Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding.
STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding (AUB) DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospitals in Rio de Janeiro and São Paulo, and private office in Rio de Janeiro. PATIENTS: Four thousand and fifty-four patients with AUB in whom hysteroscopic views were complete and the histologic result was conclusive. INTERVENTION: Four thousand and fifty-four office hysteroscopies with complete views and conclusive histologic results. The material for histologic examination was obtained through biopsy of the lesion in an outpatient unit or through the resection of the entire lesion in patients who underwent surgery. Histology was considered the "gold standard" and compared with the hysteroscopic view. MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations, 613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer. The most frequent hysteroscopic finding was endometrial polyps (31.2%). In endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95% CI 52.2%-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was 92.0% (95% CI 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy was defined as the proportion of correct results among the hysteroscopic examinations. In endometrial cancer, the sensitivity of the hysteroscopic view was 80.0% (95% CI 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV was 81.5% (95% CI 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the hysteroscopic view was normal, there were no false negatives for endometrial cancer; however, there were 37 (4.5%) false negatives for endometrial hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%) hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%, respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%, respectively). CONCLUSION: It seems that even in face of good validity of hysteroscopic view for endometrial hyperplasia and cancer, histologic study is mandatory in the presence of any lesion as the hysteroscopic view cannot completely replace the histologic study in patients with AUB.
Adult↗
Hysteroscopic resection of endometrial hyperplasia.
STUDY OBJECTIVE: To evaluate the efficacy and safety of hysteroscopic resection of endometrial hyperplasia without atypia. DESIGN: Pilot feasibility study (Canadian Task Force classification II-1). SETTING: Department of gynecology at a general hospital. PATIENTS: Seventy-three women. Intervention. Transcervical hysteroscopic endometrial resection under general or spinal anesthesia. MEASUREMENTS AND MAIN RESULTS: Efficacy of treatment was based on hysteroscopic and histologic regression of endometrial hyperplasia and subjectively assessed uterine bleeding. Safety was evaluated by adverse events. Forty-four cycling women experienced complete remission of uterine bleeding and none had persistence of endometrial hyperplasia during follow-up; four underwent hysterectomy. Atrophic endometrium was present in 24 menopausal women, one of whom underwent hysterectomy. CONCLUSION: Endometrial resection was effective in achieving regression of endometrial hyperplasia and preventing its recurrence. (J Am Assoc Gynecol Laparosc 6(2):151-154, 1999)
Adult↗
MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer.
The predictive value of MLH1 or MSH2 protein expression for the presence of truncating germline mutations was examined in benign and (pre)malignant endometrial samples from 3 patient groups: (I) 10 endometrial cancer patients from hereditary non-polyposis colorectal cancer (HNPCC) families with (n = 6) or without (n = 4) a known germline mutation; (II) 15 women from HNPCC families with (n = 7) or without (n = 8) a known germline mutation, who underwent endometrial sampling for non-malignant reasons; (III) 38 endometrial cancer patients <50 years of age, without HNPCC family history. Immunostaining for MLH1 and MSH2 was performed on paraffin-embedded sections. In group III, tumor DNA was examined for microsatellite instability (MSI) and MLH1, MSH2 and MSH6 mutation analysis was carried out. In 6/6 MLH1/MSH2 mutation carriers with endometrial cancer (group I), concordance was found between protein loss in the tumor and the corresponding mutation. In 3 MLH1 mutation carriers, MLH1 protein loss was also observed in concurrent endometrial hyperplasia. In group II, no protein loss was detected in normal endometrial tissue samples; in 3/4 patients with endometrial hyperplasia, MLH1/MSH2 protein loss was observed. In group III, protein loss was detected in 12/38 patients (9 MLH1, 3 MSH2), while in 3/11 patients with concurrent endometrial hyperplasia protein loss was also observed in the hyperplasia. MSI analysis in group III revealed 26 MSI-low and 12 MSI-high tumors. Mutation analysis in 28/38 patients showed only 1 missense MSH6 and no MLH1 or MSH2 germline mutations. In group III, loss of MLH1/MSH2 protein expression was not related to the presence of MSI or MLH1/MSH2 germline mutations. In conclusion, MLH1 or MSH2 protein loss in HNPCC-related endometrial neoplasia is strongly related to corresponding germline mutations. This relation was not clearly present in young sporadic endometrial cancer patients. Immunohistochemical pre-screening of the MLH1 and MSH2 proteins in endometrial hyperplasia or cancer can thus be helpful in HNPCC families. Frequent loss of MLH1 or MSH2 protein in endometrial hyperplasia indicates that this loss is an early event in endometrial carcinogenesis.
Adaptor Proteins, Signal Transducing↗
Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium.
OBJECTIVES: To determine whether cyclooxygenase-2 (COX-2) expression is seen in endometrial cancer, endometrial hyperplasia, and normal endometria and whether it correlates with expression of estrogen and progesterone receptors. METHODS: The study was a retrospective, IRB-approved analysis of biopsy samples from 14 patients with endometrial adenocarcinoma, 19 with endometrial hyperplasias, and 10 with normal endometrium. Excluded were samples from women with a history of pelvic radiation, NSAID use, or treatment with hormones during previous year. Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissues. Expression of COX-2, estrogen and progesterone receptors were scored according to the proportion of positive-staining cells: 1(+), <10%; 2(+), 10-50%; and 3(+), >50%. A score > or =2(+) was considered positive. Fisher's exact test and analysis of variance were used to compare proportions and continuous variables, respectively. RESULTS: Overexpression of COX-2 was seen in 4 (29%) of the endometrial cancers, 6 (32%) of the endometrial hyperplasia, and 4 (20%) of the normal endometria. These differences were not statistically significant (P = 0.90). No COX-2 expression was found in stromal tissue. Of 14 endometrial cancers, 7 (50%) expressed any COX-2, with 4 (29%) having an expression score of > or =2(+). Of 19 endometrial hyperplasias, 11 (58%) expressed any COX-2; with 6 (32%) having a score of > or =2(+). All 10 normal endometria showed only 1(+) expression. No significant differences were detected in COX-2 expression by grade or stage of cancer. Although 100% and 95% of both hyperplasia and normal endometrium samples expressed in estrogen and progesterone receptors, respectively, only 71% and 79% of endometrial cancers expressed estrogen and progesterone receptors (P = 0.01). A nonparametric trend was performed to detect a relationship, between COX-2 and estrogen receptor or progesterone receptor expression; no significant trend was found. CONCLUSIONS: In this study, the immunohistochemical analysis showed a trend toward increased COX-2 expression in endometrial cancer and hyperplasia compared to normal endometria. A larger sample size is needed to confirm these results. The increased COX-2 expression in hyperplasia may signify an early step in carcinogenesis. These findings may represent an important treatment opportunity for synergism in the hormonal therapy of endometrial cancer.
Adult↗
Differences in serum bisphenol a concentrations in premenopausal normal women and women with endometrial hyperplasia.
Exposure to endocrine disrupting chemicals (EDCs) has been raised in relation to its potential for adverse health outcomes. Bisphenol A (BPA) is an estrogenic EDC widely found in plastic products. We determined BPA concentrations in premenopausal women by an enzyme-linked immunosorbent assay and evaluated possible linkage between its contamination levels and endometrial hyperplasia, an estrogen-related disorder of the uterus. It has been implied that higher levels of BPA, which binds to estrogen receptor and plays estrogenic roles may, enhance endometrial hyperplasia. Serum BPA was detectable in all subjects and its concentrations in healthy controls with normal endometrium were 2.5 +/- 1.5 ng/ml (mean +/- SD). BPA levels in patients with simple endometrial hyperplasia with benign nature were 2.9 +/- 2.0 ng/ml and were not significantly different from the controls. Unexpectedly, BPA levels in patients with complex endometrial hyperplasia with malignant potential were 1.4 +/- 0.4 ng/ml and significantly lower compared to both control and simple endometrial hyperplasia groups. In addition, we measured the serum BPA levels in postmenopausal endometrial cancer patient (1.4 +/- 0.5 ng/ml), which were also significantly lower than control and simple endometrial hyperplasia groups. These findings suggest the presence of associations between BPA exposure and complex endometrial hyperplasia and endometrial cancer. The mode of action of BPA may be more complex than expected and the contradictory results may serve as a clue to addressing the mechanisms of linkage between occurrence of estrogen-dependent diseases and endocrine disruption.
Benzhydryl Compounds↗
Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration for endometrial hyperplasias.
BACKGROUND: To determine the biologic difference between normal endometrium and endometrial hyperplasias, the authors assessed the expression of estrogen receptors (ER) and progesterone receptors (PR) in the subjects before and after oral administration of medroxyprogesterone acetate (MPA) (Hysron-H, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan). METHODS: The authors studied the expression of ER and PR in pathologic conditions of the endometrium such as cystic, adenomatous, and atypical hyperplasias before and after MPA treatment, 600 mg daily, for 8-14 weeks, and compared this expression with that of normal endometrium. RESULTS: Stromal and epithelial components of the normal endometrium in the proliferative phase were positive for ER and PR. In the secretory phase and after MPA treatment, the epithelial component showed either negative or faint staining for ER and PR, but the stromal component showed positive staining for PR and negative or faint staining for ER. All hyperplasias exhibited ER and PR in the stromal and epithelial components, although the intensity of the staining was variable in atypical hyperplasias. After MPA treatment, in the epithelial component of cystic and adenomatous hyperplasias, down-regulation of PR was prominent, but many cells continued to express ER. The epithelial component usually was surrounded by PR-positive decidual cells. In atypical hyperplasia, many cells continued to express ER and PR in the epithelial component surrounded by both ER and PR positive stromal cells after MPA treatment. CONCLUSIONS: Among the pathologic conditions of the endometrium, cystic and adenomatous hyperplasias have mechanisms of down-regulation of PR but not ER in the glandular component after MPA treatment, whereas in atypical hyperplasia, down-regulation of ER and PR does not occur in the epithelial component. Compared with normal endometrium, the majority of endometrial hyperplasias have an impairment of down-regulation of ER in the epithelial component by MPA treatment, and atypical hyperplasia has an impairment of down-regulation of ER and PR. Endometrial hyperplasias seem to have an abnormality of down-regulatory mechanisms of sex steroid receptors in the epithelial component when treated with exogenous progesterone.
Adult↗
Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.
Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.
Adult↗