Utility of a Novel High-Sensitivity Multiplex Companion Diagnostic Test Using Formalin-Fixed Paraffin-Embedded Cell...

Formalin-fixed paraffin-embedded (FFPE) tissue is the standard material for companion diagnostic tests (CDx). Although cytological specimens can be useful, their low tumor content (TC) poses challenges. Recently, a high-sensitivity CDx, the "Lung Cancer Compact Panel (cPANEL)," with a recommended TC of 5%, was introduced into clinical practice. This CDx achieves high detection sensitivity by selecting specific genes for analysis, processing them separately, and performing sequence at sufficient depth. This approach enables the detection of mutations even when they are present in only small amounts within the sample. This study aimed to evaluate the utility of cPANEL using FFPE cell block (CB) with a low TC.

We analyzed FFPE-CB pleural fluid samples from 26 patients diagnosed with malignant pleural effusion originating from lung adenocarcinoma. TC was quantified using AI-equipped image analysis software, and samples with a TC of less than 10%-the minimum threshold for single-CDx-were selected for CDx analysis. To confirm that cPANEL has better sensitivity than single-CDx, which has high detection power, and that it is advantageous in low TC samples such as FFPE-CB, we compared the two CDx assays based on the EGFR-positive rate using samples that did not meet the TC criterion for single-CDx.

Most FFPE-CB had low TC levels, with only approximately 27% meeting the TC criteria for the widely used multi-CDx. Furthermore, over 60% of the samples fell below the 10% threshold for a single-CDx. Despite the low TC, EGFR mutations were partially detected, with cPANEL achieving a higher detection rate than that of single-CDx (68.8% vs. 50.0%).

Although cPANEL is classified as a multi-CDx, it demonstrated superior sensitivity compared with that of single-CDx. It proved effective even for FFPE-CB samples with very low TC, making it a promising tool to enhance the use of cytological samples for CDx in the future.