Sub-type Specific Genomic Mutations in sBOTs

Study Overview
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Brief Summary
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The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern. The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Detailed Description
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Introduction Borderline Ovarian Tumors (BOTs) behave indolently in the vast majority of cases and the prognosis is usually favorable. There is more evidence that two subtypes of BOTs represent a higher risk of recurrence or even progression to an invasive ovarian cancer. In case of a presentation with a micro-papillary grow pattern or when invasive implants are diagnosed the prognosis tend to be less favorable. Genome sequencing in ovarian cancer helped to differentiate two different pathways in the carcinogenesis. Low grade serous carcinomas evolving from adenofibromas or borderline tumors over non-invasive micropapillary serous borderline tumors to invasive micropapillary serous carcinoma, show frequent mutations in the Kirsten Rat Sarcoma gene (KRAS), B-Raf Kinase gene(BRAF), Erb-B2 Receptor Tyrosine Kinase 2 gene (ERBB2), Phosphatase and Tensin homolog gene (PTEN), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) and Catenin Beta 1 gene (CTNNB1). This pathway is called Type I and is characterized by a slow step-wise process. These low-grade invasive tumors are indolent and are known with a better outcome than high-grade invasive tumors. In contrast the Type II pathway development of invasive tumors is rapid and vast majority of tumors show a Tumor Protein p53 (TP53) mutation and loss of Breast Cancer type 1 susceptibility protein (BRCA1). The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern. The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Official Title
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Sub-type Specific Genomic Mutations in Serous Borderline Ovarian Tumors

Conditions
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Ovarian Neoplasm Epithelial

Intervention / Treatment
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* Genetic: genomic mutations study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paraffin embedded material from the original borderline ovarian tumor must be present and of good quality for DNA extraction. Original slides are available for central pathological review. Exclusion Criteria: Presence of invasive ovarian carcinoma.

Ages Eligible for Study
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Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| serous BOT<br>simple serous BOT ovarian tissue | Genetic: genomic mutations study<br>* Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)<br>|
| serous BOT with non-invasive implants<br>BOT ovarian tissue presenting with non-invasive implants | Genetic: genomic mutations study<br>* Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)<br>|
| sBOT with micropapillary grow pattern<br>BOT ovarian tissue presenting with micropapillary grow pattern | Genetic: genomic mutations study<br>* Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)<br>|
| serous BOT with invasive implants<br>sBOT ovarian tissue presenting with invasive implants at the time of diagnosis | Genetic: genomic mutations study<br>* Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| genetic mutations | amount and type of genetic mutations in different subgroups will be analyzed and compared between the different subgroups. Are the mutations suggestive for a type I or type II pathway differentiation? | 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low malignant potential, serous