Immunohistochemical Algorithm for the Diagnosis and Classification of Hepatocellular Carcinomas With TERT, TP53 and CTNNB1 Mutation

The presence of certain mutations in HCC, such as TERT and TP53, have a suspected or proven prognostic role in resected patients, but lack a morphological or immunophenotypic counterpart, which would allow us to define which tumours are rationally candidate for molecular biology analysis. The identification of a histological and immunohistochemical algorithm to determine which HCCs to take to NGS for prognostic purposes will save time and economic costs in the laboratory by rationalising available resources. In the future, the application of the immunohistochemical and molecular algorithm on biopsy could allow better prognosis and predictivity even before surgery/therapy.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Cancer; Hepatic Resection
• Intervention / Treatment: Diagnostic test: Immunohistochemistry and in situ hybridisation analysis

Detailed Description

The primary aim is the identification of possible associations between the biomarkers p53 and beta-Catenin and the presence of the genetic mutations TERT, TP53 and CTNNB1 identified by clinical practice, in patients undergoing hepatic resection of HCC.

The secondary objective is the identification of possible associations between the presence of biomarkers Glutamin Synthetase, Glypican-3 and HSP70 and genetic mutations identified by clinical practice, in patients undergoing hepatic resection of HCC.

STUDY DESIGN: exploratory study. It is planned to recruit approximately 100 patients, who underwent liver resection for HCC and already underwent NGS analysis (for which the mutational profile is already known). All clinical and histological data will be collected, immunohistochemistry investigations will be performed on formalin-fixed and paraffin-embedded material corresponding to that used for molecular analysis.

STUDY POPULATION: The study envisages the enrolment of 100 patients, already undergoing liver resection for HCC at the IRCCS AOU of Bologna, in the period 2020-2022, who will be retrospectively re-evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francecso Vasuri, MD; Phone Number: 0512143761; Email: francesco.vasuri2@unibo.it
• Study Contact Backup: Name: Deborah Malvi, MD; Phone Number: 0512143761; Email: deborah.malvi@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Deborah Malvi, MD; Phone Number: 0512143761; Email: deborah.malvi@aosp.bo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Patients resected for HCC
• Availability of NGS data
• Availability of paraffin material for immunohistochemistry investigations

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resected HCC patients; patients resected for HCC with NGS data, and paraffin material for immunohistochemistry analysis.	Diagnostic test: Immunohistochemistry and in situ hybridisation analysis; immunohistochemistry and in situ hybridisation analysis for several markers, including p53, beta-Catenin and albumin, but also markers considered diagnostic for HCC such as Glutamin Synthetase, Glypican-3 and HSP70, to identify a more rational diagnostic-prognostic algorithm for primary liver lesions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
associations between p53 and beta-Catenin and the presence of the genetic mutations	Identification of associations between the biomarkers p53 and beta-Catenin and the presence of the genetic mutations TERT, TP53 and CTNNB1 identified by clinical practice, in patients undergoing hepatic resection of HCC.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of associations between the presence of biomarkers Glutamin Synthetase, Glypican-3 and HSP70 and genetic mutations	Identification of associations between the presence of biomarkers Glutamin Synthetase, Glypican-3 and HSP70 and genetic mutations identified by clinical practice, in patients undergoing hepatic resection of HCC.	At baseline

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Francesco Vasuri, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Estimated): May 13, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 1, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Estimated): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Immunohistochemistry; Molecular diagnostics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: HCCimmuno_2024; 2023.0275 (Other Grant/Funding Number: Fondazione Cassa di Risparmio in Bologna)

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