Exploiting Pathogenic Tp53 Mutation for Early Diagnosis of Ovarian Cancer by Mean of Papanicolau Test

Study Overview
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Brief Summary
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The aim of the project is to corroborate them on a large retrospective cohort of HGS-EOC and confirm the possibility of identify TP53 mutations in high grade endometrioid tumors. This will consequently allow to confirm the previous results and define with a greater precision the temporal windows in which it will be possible to detect, through the TP53 analysis, tumor material by vaginal swab sampling. The results of the study will be the first step of a multiphase prospective validation program for the development of a novel approach for early diagnosis of EOC.

Detailed Description
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All participating women will be identified through the ovarian cancer audit implemented by the Oncological Network of Piedmont and Valle d'Aosta and the Clinical Epidemiology Unit of CPO Piemonte between 2015 and 2020. Women with EOC, and the center where they have been treated for the tumor, will be identified by linking the databases of the Oncological Network of Piedmont and Valle d'Aosta with those of the Prevenzione Serena project. A few clinical information from EOC patients will be collected by clinical investigators at each center using an electronic case report form (e-CRF) developed at the Mario Negri Institute. These information will include age, date of diagnosis, histological subtype and grading, tumor stage according to FIGO 2014 classification2,3, previous gynecologic conditions and surgical operations, date of Pap Test collection, and Pap Test cytological reports. Participants' data will be identified by a unique patient code.

Official Title
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Exploiting Pathogenic Tp53 Mutation for Early Diagnosis of Ovarian Cancer by Mean of Papanicolau Test

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Diagnostic Test: Patients with Ovarian cancer and pap test available


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥18 years; confirmed histologic diagnosis of HGS-EOC or high grade endometrioid tumor; presence of one FFPE primary tumor biopsy with at least 40% of tumor cells based on Hematoxylin and Eosin staining, in the archive of the Pathology Departments of the hospital centers where they have been treated; presence of one or more Pap Tests sampled up to eight years before EOC diagnosis during routine cervical cancer screening; negative history for other gynecologic malignancies; Exclusion Criteria: pap test not available in patients with ovarian cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Patients with Ovarian cancer and pap test available|Define the possibility to detect through the pap test the presence of ovarian cancer cells in vaginal smear in patients with no evidence of ginecological malignancies.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate that clonal pathogenic TP53 variants of HGS-EOC can be detected in patient-matched PAP tests | To validate the preliminary data obtained by Paracchini 14, which found that the clonal pathogenic TP53 variants of HGS-EOC can be detected in PAP tests of patient tratted by ovarian cancer performed more than two years before the diagnosis of ovarian neoplasia. Within this aim, we will calculate the detection rate and define the temporal window up to which the detection of the TP53 variant is feasible and set up the optimal experimental conditions, such as DNA quality and quantity, that will be used in the downstream steps for the assay development. | We can estimate six month to obtain pathological sample from the different hospital involved in this protocol and in the mean time to set up the laboratory procedures in large scale. | 
| Demonstrate that clonal pathogenic TP53 variants of HGS-EOC can be detected in patient-matched PAP tests | The second outcome is the evaluation of the percentage of pap test negative for cervical cancer and positive for genetic determination of ovarian neoplastic cells in pre clinic stage of ovarian neoplasia. | In the following six months the data obtained are processed. The final analisys is forecast within one year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, pap-test