Sub-type Specific Genomic Mutations in sBOTs

NCT ID: NCT03883542

Last Updated: 2023-05-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2024-04-30

Brief Summary

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

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.

Conditions

Ovarian Neoplasm Epithelial

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

serous BOT

simple serous BOT ovarian tissue

genomic mutations study

Intervention Type: GENETIC

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,

2. serous BOT tissue with non-invasive implants and

3. 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)

serous BOT with non-invasive implants

BOT ovarian tissue presenting with non-invasive implants

genomic mutations study

Intervention Type: GENETIC

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,

2. serous BOT tissue with non-invasive implants and

3. 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)

sBOT with micropapillary grow pattern

BOT ovarian tissue presenting with micropapillary grow pattern

genomic mutations study

Intervention Type: GENETIC

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,

2. serous BOT tissue with non-invasive implants and

3. 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)

serous BOT with invasive implants

sBOT ovarian tissue presenting with invasive implants at the time of diagnosis

genomic mutations study

Intervention Type: GENETIC

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,

2. serous BOT tissue with non-invasive implants and

3. 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)

Interventions

genomic mutations study

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,

2. serous BOT tissue with non-invasive implants and

3. 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)

Intervention Type: GENETIC

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: lead

Responsible Party

Stefan Cosyns

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

stef cosyns, dr

Role: PRINCIPAL_INVESTIGATOR

UZBrussel

Locations

Universitair Ziekenhuis UZBrussel

Jette, Brussels Capital, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Stefan Cosyns, Dr

Role: CONTACT

scosyns@uzbrussel.be

24776020 ext. +32

Facility Contacts

Stefan Cosyns, Md

Role: primary

Scosyns@uzbrussel.be

24776020 ext. 0032

References

Morice P, Uzan C, Fauvet R, Gouy S, Duvillard P, Darai E. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol. 2012 Mar;13(3):e103-15. doi: 10.1016/S1470-2045(11)70288-1.

Reference Type: BACKGROUND

PMID: 22381933 (View on PubMed)

Vang R, Shih IeM, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009 Sep;16(5):267-82. doi: 10.1097/PAP.0b013e3181b4fffa.

Reference Type: BACKGROUND

PMID: 19700937 (View on PubMed)

Despierre E, Lambrechts D, Neven P, Amant F, Lambrechts S, Vergote I. The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. Gynecol Oncol. 2010 May;117(2):358-65. doi: 10.1016/j.ygyno.2010.02.012. Epub 2010 Mar 7.

Reference Type: BACKGROUND

PMID: 20207398 (View on PubMed)

Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010 Mar;34(3):433-43. doi: 10.1097/PAS.0b013e3181cf3d79.

Reference Type: BACKGROUND

PMID: 20154587 (View on PubMed)

Other Identifiers

sBOT

Identifier Type: -

Identifier Source: org_study_id