Sub-type Specific Genomic Mutations in sBOTs

Ovarian Neoplasm Epithelial Clinical Trial

Official title:

Sub-type Specific Genomic Mutations in Serous Borderline Ovarian Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03883542
• Other study ID #: sBOT
• Status: Recruiting
• Start date: January 2017
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2023
• Source: Universitair Ziekenhuis Brussel
• Contact: Stefan Cosyns, Dr
• Phone: 24776020
• Email: scosyns[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Ovarian Neoplasm Epithelial
• Ovarian Neoplasms

Intervention

Genetic:
• genomic mutations study
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)

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis UZBrussel	Jette	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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