"MSI analysis in solid and liquid biopsies: the great potential of ddPCR molecular approach" EACR & Bio-Rad Webinar

Virtual Meeting, Online

30 November 2023

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15:00 CET on Zoom

This free webinar is hosted in collaboration with Bio-Rad, one of our valued EACR Industry Partners. We are delighted to welcome Matteo Curtarello from the Institute Oncology Veneto in Italy, who will talk about how MicroSatellite Instability (MSI) status predicts the clinical benefit of immunotherapy with PD-1/PD-L1 inhibitors and how this can help to find a valid alternative to currently used immunohistochemistry (IHC) typing. He will discuss published data regarding MSI analysis in solid and liquid biopsy of GastroEsophageal Adenocarcinoma (GEA) patients.

Talk Abstract

MicroSatellite Instability (MSI) phenotype is characterized by a deficiency of at least one protein of the DNA mismatch repair (MMR) system. Moreover, this condition is frequently associated to a high mutational burden (14.6–60.9 mutations/Mb) with frequent mutations in PIK3CA, ERBB3, ERBB2 and EGFR. Recent studies have shown that the MSI status predicts the clinical benefit of immunotherapy with PD-1/PD-L1 inhibitors leading to the approval of pembrolizumab for unresectable or metastatic MSI solid tumors following progression on prior therapies. The exact mechanism of the more efficient response to the immunotherapy of MSI patients is unknown; in any case, it seems that tumors with a high mutational burden (>10 mutations/Mb) express neoantigens that could render them more susceptible to an immune checkpoint blockade.

In this presentation, I would like to present published data regarding MSI analysis in solid and liquid biopsy of GastroEsophageal Adenocarcinoma (GEA) patients. GEAs include gastric as well as esophageal adenocarcinomas that are characterized by similar genetic and epigenetic molecular alterations. Recently, The Cancer Genome Atlas Research Network proposed a simple and stepwise process to characterize a GEA based on its predominant molecular profile. This approach provides prognostic information and suggests a potential benefit from targeted therapy. It is possible to distinguish four GEA subtypes based on genomic characterization: Epstein–Barr virus-positive (EBV; 9%), microsatellite instability (MSI; 22%), chromosomal instability (CIN; 50%) and genomic stable tumors (GS; 20%). Currently, MSI testing for immunotherapy decision-making is commonly performed on tissue biopsies through the assessment of the MMR proteins’ expression level by immunohistochemistry (IHC). However, about 5–11% of MSI GEAs, with a normal MMR protein staining and localization could have dysfunctional proteins due to missense mutations, leading to the erroneous exclusion of these patients from immunotherapy. Furthermore, tissue biopsies have several limitations since they could not represent the whole tumor status, especially in highly heterogeneous tumors such as GEAs, are invasive and make the longitudinal monitoring of the disease status impossible. Thus, the development of new and reliable diagnostic tools transposable also to liquid biopsy is needed. Indeed, currently it is recognized that cell-free DNA (cfDNA) gives more comprehensive information regarding tumor burden by overcoming the challenge of intratumoral heterogeneity. Taking into account the possibility for MSI patients to have a benefit from immunotherapy, the application of more sensitive molecular approaches to improve MSI detection could recover those patients who have been excluded from the proper therapeutic approach. 

In this study, aimed to find a valid alternative to currently used IHC typing, we tested different molecular approaches to analyze MSI status in formalin-fixed paraffin-embedded (FFPE) tissues DNA and in cfDNA of GEA patients. Our results highlight the molecular analysis as an optimal alternative to IHC for the diagnostic typing and suggest that the ddPCR assay can be considered as the most reliable and promising molecular approach to detect MSI in the cfDNA of GEA patients.

Speaker

Matteo Curtarello, Institute Oncology Veneto, IRCCS, Italy
Matteo Curtarello is a Biologist. He graduated with honors in Medical Biotechnology in 2004 and in Cellular and Molecular Biology in 2010 at the University of Bologna. He obtained his PhD Degree in Virology and Microbial Biotechnology in 2008 at the University of Padova. Afterwards, he finished his residency in Clinical Biochemistry in 2017 at the University of Milano.

Since 2009, Matteo Curtarello focused his research activity mainly on the metabolic effects of anti-angiogenic therapy in preclinical models of epithelial ovarian cancer (EOC). Currently, he has evaluated the concordance between molecular analysis and IHC diagnostic typing, focusing on the most important biomarkers in GEA patient’s management (MSI, HER2, p53).

Open to all, you do not need to be an EACR member to attend.

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