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

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ClinicalTrials.gov Identifier: NCT03498924
Recruitment Status : Completed
First Posted : April 17, 2018
Last Update Posted : February 11, 2020
Sponsor:
Information provided by (Responsible Party):
Tatiana Cuesta-Guardiola, Fundación Investigación Sanitaria en León

Brief Summary:
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.

Condition or disease Intervention/treatment
Endometrial Neoplasm Malignant Diagnostic Test: Measure of biomarkers in serum and endometrial tissue

Detailed Description:

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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. After discharge, the patient will be follow-up for two years in order to register the evolution of the disease.

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Study Type : Observational
Actual Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Prospective Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue Samples
Actual Study Start Date : August 1, 2017
Actual Primary Completion Date : August 1, 2018
Actual Study Completion Date : June 1, 2019

Group/Cohort Intervention/treatment
CASES
Patients with endometrial cancer
Diagnostic Test: Measure of biomarkers in serum and endometrial tissue
Blood sample and endometrial sample

CONTROLS
Matched controls without neoplasm disease
Diagnostic Test: Measure of biomarkers in serum and endometrial tissue
Blood sample and endometrial sample




Primary Outcome Measures :
  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 Outcome Measures :
  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.


Biospecimen Retention:   Samples With DNA
Serum and endometrial tissue sample of every patient


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Every patient who is treated in Hospital de Leon of endometrial disease between August 2017 and the end of the recruitment
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03498924


Locations
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Spain
Tatiana Cuesta-Guardiola
Leon, Spain, 24080
Sponsors and Collaborators
Fundación Investigación Sanitaria en León
Investigators
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Principal Investigator: Tatiana Cuesta-Guardiola, Medicine Hospital de Leon

Publications of Results:
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Responsible Party: Tatiana Cuesta-Guardiola, Principal investigator, Fundación Investigación Sanitaria en León
ClinicalTrials.gov Identifier: NCT03498924    
Other Study ID Numbers: STUDY17104
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tatiana Cuesta-Guardiola, Fundación Investigación Sanitaria en León:
tumor marker
HE4
CA125
staging
diagnosis
Endometrial Cancer
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female