Computer-Aided Diagnostics Helps Accurately Determine Different Expression Levels of Claudin-18.2 in Gastric Cancer

Determination of claudin-18.2 expression by immunohistochemistry (IHC) is a prerequisite for targeted treatment of gastric cancers (GCs) with zolbetuximab. Precise assessment of IHC expression categories, however, may be challenging and prone to interobserver variability. Computer-aided diagnosis has a high potential of improving diagnostic accuracy and reproducibility. We established a computer-aided analysis tool for claudin-18.2 positivity scoring.

Analysis steps included the identification of tumour tissue on haematoxylin-3,3'-diaminobenzidine-stained tissue microarray (TMA) slides, cell segmentation, and membranous staining intensity estimation of claudin-18.2 (clone 43-14A). We analysed 2,248 cores from 417 primary resected GCs with detailed pathological data available.

In 51.6% (1,159/2,248) of TMA cores, no stained tumour cells were detected. Among cases with claudin-18.2 expression, predominantly 1+ and 2+ cells, a minority of 3+ stained cells were found, and 2+ to 3+ staining was unevenly distributed. Utilizing the SPOTLIGHT claudin-18.2 positivity threshold, we identified 12% (187/1,555) positive cores corresponding to 2.5% (9/365) positive cases. Lower staining intensities in tumour centre cores point to intratumoural heterogeneity.

Computer-aided diagnostics helps accurately measure claudin-18.2 expression levels, allowing to precisely determine claudin-18.2 status in GC patients. Previously uncaptured categorization of staining intensities may enhance the understanding of claudin-18.2 threshold for patient stratification.