Abstract
Background: The consensus molecular subtype (CMS) classification stratifies colorectal cancer (CRC) into four groups based on gene expression, offering potential for tailored therapy. This study evaluated the feasibility of CMS classification using preoperative biopsy specimens.
Methods: This prospective pilot study enrolled eight patients with primary CRC (cT2 or deeper). In all cases, two biopsy specimens were obtained from different tumor regions during preoperative colonoscopy, using two forceps: forceps A (standard) and forceps B (jumbo). RNA yield and quality were measured, and CMS classification was conducted based on the microarray data. Concordance between a CMS classification of specimens obtained with the two forceps and the safety of the procedure were also examined.
Results: 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 with forceps A was 210.20 (105.76-589.87) ng/μl, with an 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 a RIN of 9.1 (8.6-9.6). CMS classification was successfully achieved in all samples. Notably, in three of the eight patients, the CMS classifications differed between specimens collected using the two forceps.
Conclusions: Preoperative biopsy specimens provided RNA of sufficient quality for CMS classification. However, intratumoral heterogeneity may lead to discordant classifications, and the results should therefore be interpreted cautiously. Further validation in larger cohorts is warranted.
