1229P - Selective phenotypic and genotypic evaluation of circulating glial cells for improved diagnosis of glial malignancies

Background

Accurate diagnosis plays a critical role in the effective management of glial malignancies. However, obtaining tissue specimens for histopathologic investigation carries inherent procedural risks. We present profiling of circulating glial cells (CGCs) by analyzing cell lineage-specific markers using immunocytochemistry (ICC) and EGFR gain by fluorescence In situ hybridization (FISH) on the Circulating glial cells.

Methods

In a prospective blinded study, blood specimens from patients suspected of Intracranial space-occupying lesions (ICSOL) (N=28) were collected before the invasive biopsy. CGCs were profiled using the TriNetra™ Glio assay that detects CGCs using ICC profiling of cell lineage markers (GFAP and OLIG2). CGCs were also used to perform FISH using EGFR gain. In a separate cohort comprising matched tissue and blood specimens from 44 cases (22 benign and malignant cases each), CGC profiling by ICC and EGFR FISH was performed to evaluate the concordance of profiled biomarkers on the circulating CGC population.

Results

TriNetra Glio assay successfully found CGCs in 23 out of 25 (92%) cases diagnosed with Glial malignancies. Among the 11 cases of Glioblastoma and 2 cases of astrocytoma Grade 3, EGFR amplification was found in 4 and 1 cases, respectively. In a matched cohort, EGFR copy gain was detected in tumor tissue in 8 (36%) among 22 cases of malignant glial tumors, and EGFR gain was also detectable in corresponding blood analysis. Among the remaining 14 samples with normal EGFR tissue status according to FISH, the CGCs also exhibited normal EGFR status. Further, among the 22 cases of benign tumors, there were no instances of EGFR copy gain detected by FISH on tumor tissue. All 22 samples were also negative for CGCs indicating high specificity.

Conclusions

We demonstrate a reliable method for detecting Circulating Glial Cells. This can offer valuable insights into diagnosis of suspected glial malignacies in cases where performing a biopsy is not possible. Moreover, molecular analysis of CGCs shows the potential in providing diagnostic insights that align with the current WHO classification system for the central nervous system.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Datar Cancer Genetics.

Funding

Has not received any funding.

Disclosure

F. Massoudi: Non-Financial Interests, Institutional, Advisory Board: Datar Cancer Genetics. D. Akolkar, S. Schuster, V. Datta, P. Shejwalkar, S. Patel, D.S. Patil: Financial Interests, Personal, Full or part-time Employment: Datar Cancer Genetics. R. Datar: Financial Interests, Personal, Member of Board of Directors: Datar Cancer Genetics. T. Crook: Non-Financial Interests, Personal, Advisory Board: Datar Cancer Genetics. All other authors have declared no conflicts of interest.