Feasibility of consensus molecular subtype classification of colorectal cancer using preoperative biopsy specimens: A prospective pilot study.

180 Background: Consensus molecular subtype (CMS) classification stratifies colorectal cancer (CRC) into four groups based on gene expression, offering potential for tailored therapy. However, CMS classification has mainly been validated in surgical specimens, and its feasibility in biopsy specimens remains unclear due to concerns about tissue quantity and quality. This study evaluated whether CMS classification is feasible using preoperative biopsy specimens. Methods: In this prospective pilot study, eight patients with primary CRC (cT2 or deeper) were enrolled. During preoperative colonoscopy, two biopsy specimens were obtained from different tumor regions using two forceps: forceps A (standard) and forceps B (jumbo). RNA yield and quality were measured, and transcriptome profiling was performed using Agilent microarray. CMS classification was conducted with CMScaller based on the microarray data. Concordance between CMS classifications from the two forceps and the safety of the procedure were also examined. Results: The median patient age was 59 years; five were male. Tumor sites included two right-sided colon, two left-sided colon, and four rectal cancers. All biopsy procedures were performed safely without adverse events. Median RNA yield from forceps A was 210.20 (105.76–589.87) ng/μl with RNA integrity number (RIN) of 9.2 (7.8–9.9). For forceps B, median RNA yield was 295.99 (162.23–642.17) ng/μl with RIN of 9.1 (8.6–9.6). CMS classification was successfully achieved in all samples. Notably, in three patients, the CMS classifications differed between specimens collected using the two forceps. Conclusions: Preoperative biopsy specimens provided RNA of sufficient quality for CMS classification. Nevertheless, intratumoral heterogeneity may lead to discordant classifications, necessitating careful interpretation. This pilot study enabling high-quality gene expression profiling from biopsy samples may further accelerate translational research in CRC. Clinical trial information: jRCT1042250012 .