Clinical trial NCT03498924: Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue
Official title: Prospective Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue Samples
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Endometrial Neoplasm Malignant
Keywords: tumor marker
HE4
CA125
staging
diagnosis
Endometrial Cancer
Lead sponsor: Fundación Investigación Sanitaria en León
Sponsor class: OTHER
First posted: 2018-04-17
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

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.

Eligibility 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.

Primary outcomes:
measure: The proportion of positive H-score of HE4.
timeFrame: Two years
Secondary outcomes:
measure: Concentration of HE4 in tissue correlates linearly with HE4 in serum.
timeFrame: Two years
measure: Difference in preoperative serum CA125 levels in cases and controls.
timeFrame: Two years
measure: Difference in preoperative serum HE4 levels in cases and controls.
timeFrame: Two years
measure: Disease stages
timeFrame: Two years
measure: Tissue tumor marker HE4
timeFrame: Two years
measure: Relation of the immunohistochemistry intensity in H-score with overall survival
timeFrame: Through study completion, an average of 2 years
measure: Relation of the immunohistochemistry intensity in H-score with disease-free survival
timeFrame: Through study completion, an average of 2 years
measure: Analysis of outcomes in relation to age
timeFrame: Two years
measure: Analysis of outcomes in relation to menopausal status
timeFrame: Two years
measure: Analysis of outcomes in relation to hypertension
timeFrame: Two years
measure: Analysis of outcomes in relation to diabetes
timeFrame: Two years
measure: Analysis of outcomes in relation to obesity
timeFrame: Two years
Other outcomes:
Locations:
city: Leon
country: Spain
facility: Tatiana Cuesta-Guardiola
Study officials:
affiliation: Hospital de Leon
name: Tatiana Cuesta-Guardiola, Medicine
role: PRINCIPAL_INVESTIGATOR
References:
citation: Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
citation: Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.
citation: Li X, Gao Y, Tan M, Zhuang H, Gao J, Hu Z, Wang H, Zhu L, Liu J, Lin B. Expression of HE4 in Endometrial Cancer and Its Clinical Significance. Biomed Res Int. 2015;2015:437468. doi: 10.1155/2015/437468. Epub 2015 Oct 11.
citation: Bignotti E, Ragnoli M, Zanotti L, Calza S, Falchetti M, Lonardi S, Bergamelli S, Bandiera E, Tassi RA, Romani C, Todeschini P, Odicino FE, Facchetti F, Pecorelli S, Ravaggi A. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011 Apr 26;104(9):1418-25. doi: 10.1038/bjc.2011.109. Epub 2011 Apr 5.