Benign Reproductive Tissue Analysis for Endometrial Cancer Markers
|First Received Date ICMJE||June 1, 2007|
|Last Updated Date||February 19, 2014|
|Start Date ICMJE||February 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00481754 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Benign Reproductive Tissue Analysis for Endometrial Cancer Markers|
|Official Title ICMJE||Benign Reproductive Tissue Evaluation (BRTE) Study|
-To see if women who are undergoing hysterectomy are willing to provide blood and tissue samples to help doctors identify markers that would indicate increased risk for developing endometrial cancer.
-Women between 35 and 54 years of age who will undergo hysterectomy for a non-cancerous condition, such as uterine fibroids, uterine prolapse, abnormal uterine bleeding, and others at Magee-Women's Hospital in Pittsburgh, Penn.
Our hypothesis is that silent molecular lesions , defined as molecular alterations detectable in histologically normal endometrial and ovarian tissues, represent markers of cancer risk. Loss of expression of the PTEN tumor suppressor gene is currently the leading marker of interest, based on the identification of clonal mutations in approximately 50% of endometrial cancers and their precursors and the demonstration of small foci of PTEN-null glands in approximately 40% of histologically unremarkable endometrial biopsies. This proposal outlines a pilot study that will generate data necessary to design and conduct a full-scale study to test the specific hypothesis that loss of PTEN expression in normal endometrium accounts for a substantial percentage of risk conferred by known endometrial cancer risk factors. Incessant ovulation represents one of the most widely-recognized models to explain the pathogenesis of ovarian cancer, with women who have had a high number of lifetime ovulatory menstrual cycles being at increased cancer risk because of repeated ovulation-related injury to, and repair of, ovarian surface epithelium (OSE). This extremely delicate single layer of cells exfoliates easily on handling, with the majority of cells typically being lost in routine handling, when collected post-operatively. Furthermore, the identification of early stage ovarian cancer is uncommon, and the vast majority of ovarian cancers are not associated with recognizable precursors. The lack of effective techniques for collecting and studying OSE in the laboratory represents a major barrier to molecular studies designed to uncover the etiology and early pathogenesis of ovarian cancer. This proposal will develop a collection method for OSE, and demonstrate its utility for various molecular analyses. If successful, the collection of OSE will provide the basis for larger studies aimed at identifying early molecular events in ovarian carcinogenesis.
In this pilot, we will conduct endometrial and ovarian tissues (that would otherwise have been discarded without histopathologic examination) from 125 hysterectomy and/or unilateral or bilateral oophorectomy specimens obtained from women ages 18 to 54 years who were operated on for benign indications. As an amendment to this active protocol, we propose demonstrating the feasibility of obtaining intra-operative cytobrushings of ovarian surface epithelial cells on 50 women to be accrued onto the study, which will include women having hysterectomy (or unilateral oophorectomy) alone without removal of the ovaries at the time of surgery.
We will administer a questionnaire assessing endometrial and ovarian cancer risk factors and gynecologic history; obtain blood and urine, for future use in hormone studies; and obtain carefully-mapped frozen and fixed endometrial and ovarian tissues. We will immunostain endometrial tissues to assess the presence, number, location, and size of foci containing PTEN-null glands, which represents a validated surrogate of mutations in the PTEN tumor suppressor gene. This pilot will demonstrate the feasibility of executing this complex protocol; determine the number and spacing of sections required to accurately and efficiently assess the PTEN status of the endometrium; and provide data for developing power estimates needed to propose a full-scale study with a sufficient number of subjects to test our hypothesis that PTEN abnormalities account for a substantial proportion of the risk associated with recognized epidemiologic endometrial cancer risk factors. It will assess the feasibility of performing molecular analyses on ovarian surface epithelial cells collected intra-operatively, and correlating molecular finding with known ovarian cancer risk factors. If successful, this will provide the basis for larger studies aimed at identifying early molecular events in ovarian carcinogenesi, particularly in the setting of women at increased genetic risk of ovarian cancer. The pilot itself will also provide an extremely valuable repository for future biomarker pilot studies.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Tissue Evaluation|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||163|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Age between 18 and 54 years, no use of exogenous hormones within 3 months; undergoing hysterectomy with or without removal of ovaries; and a surgical indication other than cancer. Accordingly, women referred for benign indications including: leiomyomata; adenomyosis; uterine prolapse; endometrosis; dysfunctional uterine bleeding (DUB); and endometrial hyperplasia will be included.
Evidence on gross examinatiion of the surgically removed uterus that there is a carcinoma invading the myometrium; however, post-operative diagnosis of early endometrial carcinoma will not be a cause for post-hoc exclusion after specimen and data collection. We will also exclude: women undergoing surgery for prophylactiv ovarian cancer risk reduction; women with a history of cancer (other than non-melanotic skin cancer); and women currently wearing an intrauterine device.
|Ages||18 Years to 54 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00481754|
|Other Study ID Numbers ICMJE||999906109, 06-C-N109|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||August 2013|
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