This study is to find out how well liquid biopsies work as a non-invasive alternative to other methods of finding cancer cells (such as a tissue biopsy) in patients with endometrial cancer. A liquid biopsy is a blood test that may be able to find cancer cells. Collecting and storing samples of blood and tissue from patients with endometrial cancer to study in the laboratory may help doctors learn how the cells in the blood may change during treatment for uterine cancer.

PRIMARY OBJECTIVES:

I. Compare TP53, FBXW7, and other mutated gene variant allele frequencies (VAF) in serial circulating cell free deoxyribonucleic acid (ccfDNA) samples obtained from patients with endometrial cancer subtypes during the primary treatment course, which may include pretreatment, post-surgical removal, post adjuvant treatment, and at time of recurrence.

II. Compare the findings from the liquid biopsy mutational analysis to next generation sequencing from the primary tumor.

EXPLORATORY OBJECTIVES:

I. To estimate the presence of malignant cells in the vagina before and after minimally invasive hysterectomy among patients with endometrial cancer.

II. Characterize the immune profile and single cell ribonucleic acid (RNA) sequencing (scRNAseq) profile of endometrial cancer subtypes.

III. Estimate time to progression (TTP), and investigate potential correlations between mutated gene variant allele frequency (VAF) ccfDNA samples and progression.

IV. Compare the efficacy of experimental ccfDNA assays to approved ccfDNA assay using the same samples.

OUTLINE:

Patients undergo collection of blood samples for liquid biopsy during pre-treatment consultation before hysterectomy, after hysterectomy but before starting any chemotherapy, and at the end of last chemotherapy cycle. Patients also undergo collection of tissue samples during hysterectomy. Patients may also undergo Pap smears before and after hysterectomy.

Inclusion Criteria:

• Women age 18 years and older
• Histologic diagnosis of endometrial cancer
• Candidate for primary surgical treatment or has recently had prior primary surgery
• Willing and able to provide informed consent

Exclusion Criteria:

Patients who have received prior treatment including chemotherapy or radiation therapy for endometrial cancer. Prior hormonal therapy for the treatment of endometrial cancer is allowed. Patients with prior primary surgery will be allowed to enroll in this trial if the patient has not received any chemotherapy or radiation at the time of enrollment. Note: patients with a history of other cancers may be enrolled after discussion with the PI if it is determined that they are at low risk for recurrence or metastasis.

Patients with diagnosis of uterine cancer