Changes in the management and outcome of central nervous system involvement from ovarian cancer since 1994

Objective

To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer.

Methods

The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 1982-1994 were compared with those of 20 patients treated during 1995-2010 at the same center.

Results

No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010.

Conclusion

An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer.     

nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease

Objective

nm23, a tumor metastasis suppressor gene, has been linked to protection against tumorigenesis and tumor metastasis. This study evaluated whether genetic variants in the nm23 gene were associated with susceptibility to epithelial ovarian cancer (EOC) or the clinical outcome of patients.

Methods

A case-control study was performed with 302 patients with epithelial ovarian cancer and 302 control women. According to the genotypes, the outcome in 213 EOC patients was compared. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier plots and Cox models adjusted for clinical factors.

Results

The case-control analysis showed that the rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter were not associated with the risk of developing EOC. In contrast, survival analysis showed that the rs2302254 C/T polymorphism was related to the prognosis of EOC patients. Compared with patients carrying the C/C genotype, patients carrying the T/T genotype had a shorter median PFS and median OS by Kaplan-Meier plots and Cox models adjusted for clinical factors. For rs16949649 T/C polymorphisms, Kaplan-Meier analysis indicated that patients carrying the homozygous C/C genotype had shorter PFS and OS than those carrying the T allele (T/T + T/C genotype). The Cox proportional hazard model analysis suggested that this relationship was only retained in OS when adjusted for clinical factors.

Conclusion

Our studies suggest that rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter may influence the prognosis of patients with epithelial ovarian cancer.     

Clear cell carcinoma of the ovary: a review of the literature

Objective

Different histologic types of epithelial ovarian cancer may represent different diseases with unique clinical and molecular characteristics. Clear cell carcinoma (CCC) of the ovary has been reported as having a worse prognosis than high grade serous epithelial ovarian cancer (EOC). This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian CCC.

Methods

MEDLINE was searched for all research articles published in English between January 01, 1977 and January 30, 2012 which reported on patients diagnosed with ovarian CCC. Given the rarity of this tumor, studies were not limited by design or number of reported patients.

Results

Ovarian CCC tumors represent 5-25% of ovarian cancers. Its histologic diagnosis can be challenging, resulting often times in misclassification of these tumors. Ovarian CCC tends to present at earlier stages and has been associated with endometriosis, ARID1A and PIK3CA mutations. When compared to stage-matched controls, patients with early-stage ovarian CCCs may have a better prognosis than patients with high-grade serous tumors. For those with advanced stage disease, high-grade serous histology confers a better prognosis than ovarian CCC. Patients with Stage IC-IV have a relatively poor prognosis and efforts should center in discovery of more effective treatment strategies.

Conclusions

Ovarian CCC is a biologically distinct entity, different from high-grade serous EOC. Future studies should explore the role of targeted therapies in the management of ovarian CCC.     

High-intensity focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva

Objective

To assess the efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with non-neoplastic epithelial disorders of the vulva.

Method

We reviewed 41 cases of lichen sclerosus, 38 cases of squamous cell hyperplasia, and 17 mixed cases treated by HIFU from April 2004 to July 2008 at the Women's Hospital of Zhejiang University School of Medicine. Biopsy specimens were assessed with light microscopy before and after treatment.

Results

Pruritus and signs of vulvar lesions were dramatically improved following HIFU treatment, without severe complications, and 90.23% of the patients were cured or had their symptoms improved 6 months after treatment. On light microscopy, pigmentation and epithelial structures were recovered and dermal lymphocytic infiltration was reduced. The response rates were lower and complication rates higher among lichen sclerosus than among squamous cell hyperplasia cases (P < 0.05 for both).

Conclusion

Treatment with HIFU may be safe and effective in cases of vulvar dystrophy.     

Timing of fertility preservation procedures in a cohort of female patients with cancer

Objective

Comparison of time intervals from diagnosis to chemotherapy between patients opting for embryo cryopreservation or ovarian tissue cryopreservation.

Study design

Retrospective analysis.

Setting

University hospital in the Netherlands.

Patients and methods

Thirty-five female patients undergoing fertility preservation procedures before treatment with chemotherapy for cancer. Embryo cryopreservation was performed in 12 patients and ovarian tissue cryopreservation in 23 patients. We investigated differences in time intervals (from diagnosis to start of chemotherapy) between patients opting for embryo cryopreservation and patients opting for ovarian tissue cryopreservation. We calculated time intervals between the moment of diagnosis, the moment of referral, the moment of consultation, the moment of finishing of the fertility preservation procedure and the start of chemotherapy.

Results

The median time between diagnosis and referral (median = 18 days) and between referral and consultation (median = 5 days) was comparable in both groups. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation for the time interval between consultation and cryopreservation (p = 0.001). Ovarian tissue cryopreservation was completed for half of the patients within 6 days after consultation with the gynecologist, and the hormonal stimulation for embryo cryopreservation was completed for all patients within four weeks (median = 18 days), with a median of 11 days of hormonal stimulation. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation in the time interval between fertility preservation and start of chemotherapy (median = 7 vs 19 days, p = 0.019). In sum, the total duration between diagnosis and chemotherapy was significantly shorter for ovarian tissue cryopreservation patients than for embryo cryopreservation patients (median = 47 vs 69 days, p = 0.042).

Conclusion

Embryo cryopreservation can be performed within the standard timeframe of cancer care in patients with breast cancer receiving adjuvant chemotherapy, but if delay of the start of chemotherapy is harmful, ovarian tissue cryopreservation can be done within one week.     

Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A

Objective

Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast cancer, but its effects in ovarian cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch.

Methods

The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action.

Results

Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and bcl-2 proteins.

Conclusions

Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3.     

Ovarian cancer patient surveillance after curative-intent initial treatment

Objective

Patient surveillance after potentially curative treatment of ovarian carcinoma has important clinical and financial implications for patients and society. The optimal intensity of surveillance for these patients is unknown. We aimed to document the current follow-up practice patterns of gynecologic oncologists.

Methods

We created four idealized vignettes describing patients with stages I-III ovarian cancer. We mailed a custom-designed survey instrument based on the vignettes to the members of the Society of Gynecologic Oncologists (SGO). SGO members were asked, via this instrument, how often they requested 11 discrete follow-up evaluations for their patients for the first 10 postoperative years after treatment with curative intent.

Results

We received 283 evaluable responses (30%) from the 943 SGO members and candidate members. The most frequently performed items for each year were office visit, pelvic examination, and serum CA-125 level. Imaging studies such as chest X-ray, abdominal-pelvic CT, chest CT, abdominal-pelvic MRI, and transvaginal ultrasound were rarely recommended. There was marked variation in the frequency of use of most tests. There was a decrease in the frequency of testing over time for all modalities.

Conclusion

This dataset provides detailed documentation of the self-reported surveillance practices of highly credentialed experts who manage patients with ovarian cancer in the 21st century. The optimal follow-up strategy remains unknown and controversial. Our survey showed marked variation in surveillance intensity. Identifying the sources of this variation warrants further research.     

Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction

Objective

GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma.

Materials and methods

Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined.

Results

There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p = 0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p = 0.01).

Conclusion

Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction.     

Green tea for ovarian cancer prevention and treatment: a systematic review of the in vitro, in vivo and epidemiological studies

Objective

This systematic review was conducted to examine the effects of green tea or green tea components on the prevention and progression of epithelial ovarian cancer.

Methods

Using Medline, EMBASE and SciVerse (last researched: July 2011), we retrieved 22 articles including 5 epidemiological studies.

Results

In epithelial ovarian cancer cell lines, green tea and green tea components have been shown to downregulate the expression of proteins involved in inflammation, cell signalization, cell motility and angiogenesis. Green tea and green tea components would induce apoptosis and could potentiate the effects of cisplatin, a chemotherapeutic agent. In human observational studies, significant associations between green tea intake and both decreased ovarian cancer occurrence and better prognosis were reported.

Conclusions

Available literature suggests potential molecular targets for green tea in ovarian cancer treatment and also provides data supporting the clinical evaluation of the role of green tea or green tea components in ovarian cancer prevention and treatment.     

Novel nanotechnology approaches to diagnosis and therapy of ovarian cancer

Objective

Ovarian carcinoma is the leading cause of death from gynecologic malignancies, which is a direct outcome of missing its diagnosis at an early stage. Approximately 75% of ovarian cancer patients are initially diagnosed with disseminated intra-abdominal disease (stages III-IV) when ~ 30% of patients have a 5-year survival rate. In addition to the challenge of early detection of ovarian cancer, its therapy presents several challenges including the route of therapy, resistance to therapy with recurrence of cancer, and specific targeting of ovarian cancer to reduce cytotoxic side effects.

Methods

We reviewed recent literature employing nanotechnology approaches to diagnosis and therapy of ovarian cancer.

Results

Recent innovations in nanotechnology with applications in cancer diagnostics and therapy help circumvent many pre-existing problems with conventional chemotherapy and present new ways of diagnosis and therapy.

Conclusions

Nanotechnology has promising potential in enhancing early detection of ovarian cancer and treatment of recurrent disease.     

Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: a meta-analysis

Objective

To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC).

Methods

From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria.

Results

Heterogeneity tests demonstrated significant between-study variation (I² = 92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I + II; HR; 1.17, 95% CI; 1.01-1.36, stage III + IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86).

Conclusion

This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.     

Uterine artery embolization for fibroids does not have adverse effects on ovarian reserve in regularly cycling women younger than 40 years

Objective

To evaluate the impact of uterine artery embolization (UAE) for fibroids on ovarian reserve in women younger than 40 years.

Design

Prospective study.

Setting

University-based reproductive endocrinology unit.

Patient(s)

Twenty regularly cycling women aged 33-39 years undergoing UAE for fibroids. All had cycle day 3 FSH levels <10 mIU/mL.

Intervention(s)

Measurements of serum FSH and E₂ levels and of the total ovarian volume and antral follicle number by transvaginal ultrasonography on day 3 of the menstrual cycle preceding UAE and on day 3 of the cycles occurring in months 3, 6, and 12 after UAE.

Main outcome measure(s)

Preprocedural and postprocedural hormone levels, ovarian volumes, and antral follicle numbers.

Result(s)

There were no significant changes from baseline in the mean day 3 FSH and E₂ levels, ovarian volume measurements, and antral follicle numbers measured at 3, 6, and 12 months after UAE.

Conclusion(s)

Although this study might be not sensitive enough to conclude that UAE for fibroids does not interfere with a woman's ovarian status, these data indicate that in this series of reproductive-aged women UAE did not have short- or mid-term effects on ovarian reserve as assessed by hormonal and sonographic parameters.     

Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors

Objective

Epithelial ovarian carcinoma (OvCa) is rarely detected early, and it is also difficult to determine whether an adnexal mass is benign or malignant. Previously, we noted differences in methylation patterns of cell-free plasma DNA (cfpDNA) in women without disease compared to patients with OvCa. In this work, we investigated whether methylation patterns of cfpDNA can differentiate between benign and malignant tumors.

Methods

Methylation patterns in cfpDNA were determined in three cohorts (30 samples each) using a microarray-based assay (MethDet 56). Principal component analysis, supervised clustering, linear discrimination analysis, and 25 rounds of 5-fold cross-validation were used to determine informative genes and assess the sensitivity and specificity of differentiating between OvCa vs. healthy control (HC), benign ovarian disease (mostly serous cystadenoma, BOD) vs. HC, and OvCa vs. BOD samples.

Results

Differential methylation of three promoters (RASSF1A, CALCA, and EP300) differentiated between OvCa vs. HC with a sensitivity of 90.0% and a specificity of 86.7%. Three different promoters (BRCA1, CALCA, and CDKN1C) were informative for differentiating between BOD vs. HC, with a sensitivity of 90.0% and a specificity of 76.7%. Finally, two promoters (RASSF1A and PGR-PROX) were informative for differentiating between OvCa vs. BOD, with a sensitivity of 80.0% and a specificity of 73.3%.

Conclusions

This proof-of-principle data show that differential methylation of promoters in cfpDNA may be a useful biomarker to differentiate between certain benign and malignant ovarian tumors.

Research Highlights

? Methylation patterns in cell-free DNA from blood can detect ovarian tumors ? These patterns are different in patients with benign and malignant tumors ? Methylation of blood DNA can be used for differential diagnosis of ovarian cancer     

Papel de p16 en lesiones preinvasivas e invasivas de cáncer de cuello uterino. Aplicación de la técnica a citología convencional

Introduction

Detection of p16 expression by immunohistochemistry and immunocytochemistry is a good standard for the identification of high-grade cervical epithelial lesions and low-grade lesions with DNA HPV viral integration (with a tendency for progression).

Material and methods

We evaluated p16 expression in 58 HPV-positive cervical biopsies and 53 conventional cytological samples that tested HPV-positive with immunohistochemical and immunocytochemical techniques.

Results

All high-grade lesions were positive for p16 while only some of the low-grade lesions were positive. The results obtained in histological samples could be extrapolated to cytological samples from the same patients.

Conclusions

p16 expression in conventional cytology provides similar results to those in histological samples.     

Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer

Introduction

Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS).

Methods

A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS.

Results

One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range = 0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n = 51), thrombocytopenia (n = 45), and neuropathy (n = 18). There were no differences detected in PFS or OS between groups.

Conclusions

There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans.     

Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors

Objective

Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized.

Methods

We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families.

Results

In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed.

Conclusion

The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.     

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan

Objective

To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).

Methods

The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).

Results

The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.

Conclusions

Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.     

A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma

Objective

To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates.

Methods

Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m² on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m² on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles.

Results

The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naïve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naïve and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples.

Conclusions

Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.     

A modified triple incision technique for women with locally advanced vulvar cancer: a description of the technique and outcomes

Objective

To investigate the differentiation conditions of bone marrow mesenchymal stem cells (BMSCs) into endometrial epithelial cells and to confirm the effect of 17β-estradiol in this process.

Study design

BMSCs were cultured alone or co-cultured with endometrial stromal cells (EStCs) in control/differentiation medium (17β-estradiol, growth factors) and were co-cultured with EStCs in different concentrations of 17β-estradiol. Flow cytometry and immunocytochemistry were used to identify the isolated cells. Real-time RT-PCR and immunofluorescence were used to test the expression of epithelial cell markers.

Results

The epithelial markers cytokeratin-7, cytokeratin-18, cytokeratin-19, and epithelial membrane antigen were elevated in real-time RT-PCR (P < 0.05), and cytokeratin was strongly positive in immunofluorescence analysis in the differentiated BMSCs. Cytokeratin-7 and cytokeratin-19 expression levels were highest in the 1 × 10⁻⁸ mol/L 17β-estradiol group, as shown in real-time RT-PCR (P < 0.05).

Conclusion

BMSCs could be differentiated in the direction of endometrial epithelial cells in appropriate conditions in vitro: 17β-estradiol may play a key role in stimulating BMSCs’ epithelial differentiation in the process of endometriosis.

Condensation

Bone marrow mesenchymal stem cells can differentiate in the direction of endometrial epithelial cells in a certain microenvironment and appropriate concentration of 17β-E₂ can facilitate this differentiation.