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NCT Number: NCT03498924

Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue

Endometrial cancer is the most common malignant tumor of the female genital tract in our means. The diagnosis is made by endometrial biopsy sampling with anatomopathological analysis which pinpoints the cell line and the level of cell differentiation. Its treatment is surgical with adjuvant treatment (chemotherapy or radiotherapy) besides, depending on the staging. Thus far, in the first diagnosis it is only request the tumor marker CA125 in serum, but there are studies that identify the HE4 protein in blood as a feasible marker for endometrial cancer. Furthermore, the staging changes the surgical and the adjuvant treatment: in its early stages, surgery is based on hysterectomy and double adnexectomy, however, in later stages it is necessary to add pelvic and paraaortic lymphadenectomy with the associated comorbidity. This makes extremely important that the preoperative diagnosis is accurate. The aim of this study is to identify and characterize the HE4, Ki67, p53 and other potential biomarkers in endometrial tissue in order to diagnose patients with disease only with a biopsy. Moreover, the investigators are searching for connections among these markers and prognostic factors such as grade of cell differentiation, cell line, lymphatic affectation, tumor stage or even features as survival or disease free survival.

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Key information

Conditions

Endometrial Neoplasm Malignant Disease Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Tatiana Cuesta-Guardiola

León, 24080, Spain

About this study

List of abbreviations:

  • HE4: Human Epididymis Protein 4
  • CA125: Carbohydrate Antigen 125
  • Ki67: antigen KI67
  • EC: Endometrial Cancer
  • CT: Computed Tomography
  • NMR: Nuclear Magnetic Resonance
  • FIGO: International Federation of Gynecology and Obstetrics

The purpose of this study is:

  • The proportion of positive H-score of HE4, as quantified in endometrial tissue. It is significantly higher in patients with endometrial cancer than in non-EC patients.
  • Percentage of HE4, CA125 and other markers positives in cases and controls.
  • Concentration of HE4 in tissue, as measured by H-score, correlates linearly with HE4 concentration in serum, as measured in terms of ppmol/l.
  • Differences in serum CA125 levels between cases and controls.
  • Quantification of tissue tumor markers of EC patients, per disease stages.
  • Relation of the immunohistochemistry intensity with survival and disease-free survival times.
  • Analysis of other risk factors adjusting for known variables like age, menopausal status, hypertension, diabetes or obesity.
  • Feasibility of the technique.

Steps in the study:

  • Patients enter the study when a diagnosis of endometrial cancer is done. As it is ordinary in the clinical practice the diagnosis is made with an endometrial tissue sample taken in the office which is afterwards studied by a pathologist, who makes the final diagnosis.
  • Patients undergo the regular preoperative study with pelvic ultrasound, CT and/or NMR for the extension study, blood tests and the preanaesthetic consultation. As it is registered in the protocol of Endometrial Cancer Treatment.
  • Then a matched control is selected from the group of patients that are going to be hysterectomized for other non-malignant reasons (abdominal way, vaginal, or laparoscopic way). Variables considered for matching are: age (variability of five years), pre or postmenopausal status, hypertension, obesity and diabetes.
  • Every patient then is asked for accept and sign the informed consent. The next step is to prepare the patient for the surgery. In this moment the serum sample is taken. Subsequently the surgery will be performed.
  • Then the anatomopathological study is conducted over the preoperative tissue sample. HE4 marker in endometrial tissue is defined by H-Score while Ki67 and p53 are defined as usual. Although Ki67 is matched in > or <25% of expression instead of 14% as it is made in breast cancer tissue samples.
  • After discharge, the patient will be follow-up for two years in order to register the evolution of the disease.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female
  • Of legal age (≥ 18 years)
  • Wish to participate in the research study and sign consent forms voluntarily
  • Patients diagnosed of endometrial cancer derived to hysterectomy

Exclusion criteria

  • Patients that underwent surgery for other malignant pathologies, whether for ovarian carcinoma, cervical carcinoma or uterine sarcoma.

Treatment and study plan

Measure of biomarkers in serum and endometrial tissue

Diagnostic Test

Blood sample and endometrial sample

Primary outcomes

  1. The proportion of positive H-score of HE4.

    Time frame: Two years

    HE4 quantified in endometrial tissue is significantly higher in patients with endometrial cancer than in non-EC patients

Secondary outcomes

  1. Concentration of HE4 in tissue correlates linearly with HE4 in serum.

    Time frame: Two years

    Comparison of tissue H-score with ppmol/L in serum

  2. Difference in preoperative serum CA125 levels in cases and controls.

    Time frame: Two years

    Measured in terms of U/mL

  3. Difference in preoperative serum HE4 levels in cases and controls.

    Time frame: Two years

    Measured in terms of ppmol/L

  4. Disease stages

    Time frame: Two years

    FIGO stages: postsurgical classification drawn up to define the extent of spread of genital cancer

  5. Tissue tumor marker HE4

    Time frame: Two years

    H-score determination: Immunohistochemistry results can be evaluated by a semiquantitative approach used to assign an H-score (or "histo" score) to tumor samples. Cytoplasmic staining will be graded for intensity (0-negative, 1-weak, 2-moderate and 3-strong) and the percentage of positive cells was scored as 0 (0%), 1 (1-10%), 2 (11-50%) and 3 (51-100%).

    Single scale with scores 0-9 will be obtained by multiplying the intensity and the percentage staining score, and a total score will be calculated by grouping score 0 in total score 0, 1-3 in total score 1, 4-6 in total score 2 and 7-9 in total score 3.

    The assumption is that as higher is the score the level of cell differentiation would be minor.

  6. Relation of the immunohistochemistry intensity in H-score with overall survival

    Time frame: Through study completion, an average of 2 years

    HE4 biomarker measured with H-score in endometrial tissue, explained in outcome 5, in relation to length of time of survival

  7. Relation of the immunohistochemistry intensity in H-score with disease-free survival

    Time frame: Through study completion, an average of 2 years

    HE4 biomarker measured with H-score in endometrial tissue, explained in outcome 5, in relation to length of time after primary treatment that the patient survives without any signs or symptoms of that cancer.

  8. Analysis of outcomes in relation to age

    Time frame: Two years

    Age of patients is one of the known risk factors for EC, we are going to analysis the results of the study with this variable. As elder the relative risk is higher though there is no accurate cut-off point.

  9. Analysis of outcomes in relation to menopausal status

    Time frame: Two years

    Menopausal status is determined by questionnaire during the preoperative consultant. It is another risk factor for EC, the postmenopausal status has higher relative risk than premenopausal status.

  10. Analysis of outcomes in relation to hypertension

    Time frame: Two years

    Hypertension is diagnosed previously to surgery as Blood Pressure over 140/90 mm Hg in several measures. There is a known high relative risk of EC in patients diagnosed with hypertension.

  11. Analysis of outcomes in relation to diabetes

    Time frame: Two years

    Diabetes is a disease previously diagnosed by high glucose levels in blood. There is a known high relative risk of EC in patients diagnosed with diabetes.

  12. Analysis of outcomes in relation to obesity

    Time frame: Two years

    Obesity is defined as BMI >27 kg/m2. There is a known high relative risk of EC in patients diagnosed with obesity.

Sponsors and collaborators

Lead sponsor

Fundación Investigación Sanitaria en León

Other

Registry information

Official study title

Prospective Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue Samples

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Apr 17, 2018
Registry last updated
Feb 11, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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