Molecular Staging of Endometrial Cancer

NCT00340808CompletedOBSERVATIONAL

Summary

This study, sponsored by NCI and the Gynecologic Oncology Group (GOG), will collect tissue samples from women with cancer of the endometrium (lining of the uterus). Researchers will use the samples to learn more about endometrial cancer and develop new treatments and methods of prevention. Women with endometrial cancer who are suitable candidates for surgery and who have not had prior retroperitoneal surgery or pelvic or abdominal radiation therapy may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, and endometrial biopsy (surgical removal of a small tissue sample) or dilation and curettage (D \& C). Participants will undergo hysterectomy (surgery to remove the uterus) along with removal of both fallopian tubes and ovaries. This is the standard surgical treatment for endometrial cancer. Lymph nodes in the pelvis near the main blood vessel in the abdomen are also removed to determine if the disease has spread to these nodes. If cancer is found involving other sites, the cancer in those areas may also be removed; examination of the tissues will determine if further therapy beyond surgery is needed. Before surgery, patients will complete a 20-minute questionnaire that includes questions about their background, reproductive history, menstruation and menopause, certain surgeries, birth control pills and hormone replacement therapy, other drugs and medicines, weight and height, smoking, medical history, and family history of cancer. Some of the tissue removed during surgery, plus a urine sample collected from a catheter bag during surgery, and blood drawn before surgery and at follow-up visits 6 weeks and 3 years after surgery, will be sent to the GOG Tissue Bank in Columbus, Ohio. This bank stores, processes, and distributes biological specimens from patients that agree to participate in studies conducted by the GOG. Patients will have follow-up visits 6 weeks after surgery, then every 6 months for the next 2 years, followed annually for the next 7 years, for a total 10-year follow-up. The visits will include an examination and questions about health status and treatments received between visits. Patients whose cancer returns or worsens will undergo another tumor biopsy, if possible, at that time.

Key Facts

Lead Sponsor

National Cancer Institute (NCI)

Enrollment

5492

Start Date

2004-03-19

Completion Date

2020-06-30

Study Type

OBSERVATIONAL

Official Title

Integration of an Epidemiologic Questionnaire Into Gynecologic Oncology Group Trials: First Project, Protocol 210

Conditions

Endometrial Cancer

Eligibility

Age Range

18 Years+

Sex

FEMALE

* INCLUSION CRITERIA:
* Patients with endometrial carcinoma diagnosed by an endometrial biopsy or dilation and curettage who will undergo full surgical staging; all stages, grades and histologic subtypes will be eligible.
* Patients must be suitable candidates for surgery. Patients may also be entered on GOG-2222 (LAP2).
* Patients who have signed an approved Informed Consent.
* Patients who have met the pre-entry requirements specified in the Study Parameters.
* Patients with a prior malignancy (at least 5 years since diagnosis) with no current evidence of disease.

EXCLUSION CRITERIA:

* Patients not considered suitable candidates for surgery.
* Patients who have had prior retroperitoneal surgery.
* Patients who have received prior pelvic or abdominal radiation therapy.
* Patients who are pregnant.

Outcome Measures

Primary Outcomes

Breast, colorectal, endometrial, and ovarian cancers

Time frame: Baseline 1992-1993 with 10 years of follow-up (1992-2003)

Locations

University of Oklahoma, Norman, United States

Linked Papers

2021-01-08

The presence of an endometrioid component does not alter the clinicopathologic profile or survival of patients with uterine serous cancer: A gynecologic oncology group (GOG/NRG) study of 934 women

While most cases of endometrial cancer can readily be classified as pure endometrioid, pure serous, or another type, others show an apparent mixture of serous and endometrioid components, or indeterminate serous versus endometrioid features. Since serous histology carries a worse prognosis than endometrioid, Gynecologic Oncology Group protocol GOG-8032 was established to examine whether the presence of a non-serous component is a favorable feature in an otherwise serous cancer. 934 women with serous cancer were prospectively identified among a larger group enrolled in GOG-0210. Six expert gynecologic pathologists classified each case as pure serous (SER, n=663), mixed serous and endometrioid (SER-EM-M, n=138), or indeterminate serous v. endometrioid (SER-EM-I, n=133) by H&E morphology. Follow-up data from GOG-0210 were analyzed. The subgroups did not differ on BMI, race, ethnicity, lymphovascular invasion, cervical invasion, ovary involvement, peritoneal involvement, omental involvement, FIGO stage, or planned adjuvant treatment. SER-EM-M patients were younger (p=0.0001) and less likely to have nodal involvement (p=0.0287). SER patients were less likely to have myoinvasion (p=0.0002), and more likely to have adnexal involvement (p=0.0108). On univariate analysis, age, serous subtype, race, and components of FIGO staging predicted both progression-free and overall survival. On multiple regression, however, serous subtype (SER, SER-EM-M, or SER-EM-I) did not significantly predict survival. There were few clinicopathologic differences between cases classified as SER, SER-EM-M, and SER-EM-I. Cases with a mixture of serous and endometrioid morphology, as well as cases with morphology indeterminate for serous v. endometrioid type, had the same survival as pure serous cases. NCT#: NCT00340808.

2019-12-13

Overexpression of enhance of Zeste homolog 2 (EZH2) in endometrial carcinoma: An NRG Oncology/Gynecologic Oncology Group Study

Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that mediates epigenetic silencing of tumor suppressor genes. It is commonly over-expressed in several solid tumors and has been shown to be a prognostic biomarker. We investigated patterns of EZH2 expression in endometrial cancer. Evaluation of EZH2 expression was completed on both early and advanced stage endometrioid adenocarcinoma tissues and a subset of matched normal mullerian tissue samples, from participants enrolled in Gynecologic Oncology Group (GOG) protocol 210, using real time reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB) analysis. Non-parametric methods were used to assess differences in mRNA and protein expression respectively with known clinical/pathologic prognostic factors. Survival analysis was performed using techniques including Cox proportional hazards (PH) model to evaluate differences in progression free survival (PFS) and overall survival (OS) based on EZH2 expression. Eighty-seven patient samples were analyzed that included 60 tumors and 27 matched-normal tissue specimens. EZH2 mRNA (p < .0001) and protein expression (p < .0001) in tumor specimens were significantly higher than in matched-normal tissue. In primary tumors, EZH2 protein expression was associated with lympho-vascular space invasion (LVSI, p = .044), and EZH2 mRNA expression was associated with age (p = .037). Differences in EZH2 expression between primary tumors and matched normal tissue were not associated with other known clinical and pathologic factors. However, there did appear to be a trend toward decreased progression-free survival among patients with high EZH2 expression levels. Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. However, there were no statistically significant differences in survival associated with EZH2 expression in patients with endometrial cancer. NCT #: NCT00340808.

Linked Investigators

David G. Mutch

Leslie Randall

Molecular Staging of Endometrial Cancer