Molecular Biomarkers Predicting Early Development of Endometrial Carcinoma

Molecular Biomarkers Predicting Early Development of Endometrial Carcinoma: A Pilot Study

Endometrial carcinoma represents the most common gynaecological cancer and the sixth most frequent cancer among women worldwide. The 5-year survival of patients with stage I endometrial carcinoma is 75%-88% versus 50% for stage III or 15% for stage IV disease. Therefore, early detection could improve survival rates. Specifically, in the most prevalent, type 1 endometrial cancer develops from hyperplastic endometrium. The aim of the study was to evaluate the utility of cancer gene mutations from endometrial biopsies towards predicting synchronous or metachronous development of malignant lesions. The aim of the study was to evaluate whether endometrial biopsies could already carry mutations in cancer genes useful for predicting or anticipating subsequent cancer development

Study Overview

• Status: Recruiting
• Conditions: Cancer of Endometrium

• Study Type: Observational
• Enrollment (Anticipated): 8

Contacts and Locations

• Study Contact: Name: Gennaro Scutiero, MD; Phone Number: +390532236657; Email: gennaro.scutiero@unife.it

Study Locations

• Italy
  • Ferrara, Italy
    • Recruiting
    • Section of Obstetrics and Gynecology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
    • Contact: Gennaro Scutiero, MD; Phone Number: +390532236576; Email: gennaro.scutiero@unife.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Women with endometrial cancer and previous negative endometrial sample.

Description

Inclusion Criteria:

• age > 18 years old
• patients subjected to endometrial biopsies with previous histopathologically negative and subsequent histopathologically positive for endometrial carcinoma
• patient informed consent

Exclusion Criteria:

- Endometrial carcinoma patients without a previous non-tumour biopsy were excluded

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutation analyses on matched samples from female patients with a previous endometrial biopsy negative for cancer, followed by a subsequent biopsy positive for cancer	Mutation analyses performed on DNA isolated from formalin fixed, paraffin embedded samples retrieved for each patient by sequencing a panel of fifty genes (ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, VHL) both on non-cancerous biopsies and on matched endometrial carcinoma biopsies.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Integration of molecular results with clinico pathological data	Integration of molecular results with clinico pathological data	1 year

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara
• Investigators: Principal Investigator: Gennaro Scutiero, MD, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

Publications and helpful links

General Publications

• Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155. Erratum In: Cancer Res. 2014 Jul 15;74(14):4006.
• Bakkum-Gamez JN, Wentzensen N, Maurer MJ, Hawthorne KM, Voss JS, Kroneman TN, Famuyide AO, Clayton AC, Halling KC, Kerr SE, Cliby WA, Dowdy SC, Kipp BR, Mariani A, Oberg AL, Podratz KC, Shridhar V, Sherman ME. Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons. Gynecol Oncol. 2015 Apr;137(1):14-22. doi: 10.1016/j.ygyno.2015.01.552. Epub 2015 Feb 10.
• Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113. Erratum In: Nature. 2013 Aug 8;500(7461):242.
• Suhaimi SS, Ab Mutalib NS, Jamal R. Understanding Molecular Landscape of Endometrial Cancer through Next Generation Sequencing: What We Have Learned so Far? Front Pharmacol. 2016 Nov 1;7:409. doi: 10.3389/fphar.2016.00409. eCollection 2016.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 17, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: biomarkers; endometrial cancer; cancer gene mutations
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: 170578

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No