Noninvasive detection of microsatellite instability in patients with endometrial cancer

Abstract

The analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC).Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients

ROLE OF cfDNA AND ctDNA TO IMPROVE THE RISK STRATIFICATION AND THE DISEASE FOLLOW-UP IN PATIENTS WITH ENDOMETRIAL CANCER: TOWARDS THE CLINICAL APPLICATION

“…VAFs were found higher in tumours with high-risk characteristics. These data are in line with previous studies which demonstrated a high ctDNA content linked to high risk or advanced endometrial tumours (19,21,23,26,36). Accordingly, we found that patients with detectable levels of ctDNA at surgery had significantly shorter DFS and DSS times, although with no independent value over the rest of clinical variables, probably due to the strong correlation with the other risk factors under study.…”

“…Although few studies have been published focusing on the value of liquid biopsy-based approaches in EC, they showed promising results (17,18). For instance, higher levels of cfDNA have been associated to high risk tumours (19)(20)(21)(22)(23)(24)(25). Moreover, Bolivar et al have shown that high levels of cfDNA correlate with worse disease free survival (DFS) and disease specific survival (DSS) (23).…”

“…Moreover, Bolivar et al have shown that high levels of cfDNA correlate with worse disease free survival (DFS) and disease specific survival (DSS) (23). Regarding the specific tumour derived cfDNA (ctDNA), our group reported around 40% of patients with EC with detectable levels of ctDNA at surgery, being the patients with the higher risk of recurrence those with higher levels of ctDNA (19).…”

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

“…Adding microsatellite instability (MSI) loci to the gene panel can help to better define MMRd cases, as shown in recent studies on uterine aspirates. 53 , 54 p53 status in tumour samples was assessed using immunohistochemistry, which is commonly used in pathology laboratories as an acceptable surrogate marker for TP53 mutation status. Around 8% of cases were misclassified comparing p53 immunohistochemistry and TP53 mutations in a study evaluating 168 cases from five centres after consensus review.…”

Molecular Profiling of H-MSI/dMMR/for Endometrial Cancer Patients: “New Challenges in Diagnostic Routine Practice”

“…A dedicated analysis software integrates a fluorescent signal in an easily managed report where the MSI score is automatically calculated. Thanks to easily managing analytical procedures, the Easy PGX MSI kit is routinely employed in the diagnostic workflow of Italian institutions (26.0%) where it has been elected as a referral diagnostic tool for MSI analysis in EC patients as shown by data of an Italian survey [48]. Several studies demonstrated that this approach is suitable for MSI status evaluation in EC patients.…”