Abstract 147P
Background
The tumor-agnostic indication of immune checkpoint inhibitors to treat cancers with mismatch repair deficiency (dMMR)/microsatellite instability (MSI) increased the demand for such tests beyond Lynch syndrome. International guideline recommendations accept immunohistochemistry (IHC) for dMMR or molecular techniques (PCR, NGS) for MSI status determination tests equal, although there are scattered reports contradicting to this presumption.
Methods
We have directly compared four protein MMR immunohistochemistry to MSI Pentaplex PCR tests in a large cancer patient cohort (n=1306) of our diagnostic center where the two tests have been run parallel in 703 cases.
Results
We have found a high discrepancy rate (19.3%) of the two tests, independent of the tumor types. The MSI PCR sensitivity for MMR IHC status was found to be low (41.1%) with relatively low positive (91.6%) and negative (80.5%) predicting values. Therefore, the correlation of the two tests was low (kappa<0.7). During analysis of the possible contributing factors of this poor performance, we have excluded low tumor percentage of the samples, but identified dMMR phenotypes (classic versus non-classic or unusual) as possible contributors, since the sensitivities of PCR were very different (62.7%, 37.2%, 5.1%, respectively).
Conclusions
Our study challenges the perception that the MSI PCR and MMR IHC are equal predictive tests which might have clinical relevance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
102P - Dynamic profiling of ctDNA in HER2-alterated advanced NSCLC treated with pyrotinib and apatinib: Exploratory biomarker analysis from a phase II trial
Presenter: Yucheng Dong
Session: Poster session 08
103P - Epigenetic regulated genes enhanced fragmentomics-based model for early-stage lung cancer detection
Presenter: Yadong Wang
Session: Poster session 08
104P - The development of a classifier of somatic copy number alteration burden in liquid biopsy with potential clinical impact in advanced non-small cell lung cancer (NSCLC)
Presenter: Laura Bonanno
Session: Poster session 08
105P - Plasma ctDNA dynamics as clinical response biomarker for NSCLC: A systematic review and meta-analysis
Presenter: Luís Leite
Session: Poster session 08
106P - Longitudinal molecular characterization in plasma of EGFR mutant non-small cell lung cancer (NSCLC) experiencing early progression (EPD) on first-line osimertinib (Osi)
Presenter: Laura Bonanno
Session: Poster session 08
107P - Germline pathogenic variants identified in tissue- and blood-based whole exome sequencing in advanced solid tumors
Presenter: Takeshi Kuwata
Session: Poster session 08
108P - Assessing molecular characteristics in a large cohort of anal squamous cell carcinoma patients
Presenter: Cristina Smolenschi
Session: Poster session 08
109P - Development and validation of a digital PCR assay for detection and monitoring of universally methylated circulating tumor DNA in patients with high-grade sarcoma
Presenter: Elisabeth Ashton
Session: Poster session 08
110P - 13-plex non-invasive genotyping in HPV related cancers in the MOSCATO trial
Presenter: Elise Rupp
Session: Poster session 08
111P - Leveraging circulating tumor DNA sequencing for first-line cancer treatment: Insights from two prospective precision medicine studies
Presenter: Veronique Debien
Session: Poster session 08