801 Background: Small bowel cancer (SBC) account for less than 1% of all cancers. Jejunal and ileal adenocarcinoma (JIAC) is often considered as colorectal adenocarcinoma (CRAC), even some comparative studies have revealed the differences on immunohistochemical and genomic analyses. Small bowel malignancy project is currently underway in Japan and the first Japanese classification for JIAC only has recently been developed. Methods: A total of 70 patients with JIAC were recruited from Hamamatsu University Hospital (HUH) and associated hospitals, and 182 patients with CRAC were recruited from HUH. 55 JIACs and 192 CRACs were used to construct tissue microarray blocks (tumor purity ≥ 50% under microscopy). Immunohistochemical analysis were performed using 32 primary antibodies. 8 mismatch repair proficient (pMMR)-JIACs were selected for multiregional whole exome sequencing (WES) analysis, and 4 pMMR-JIACs were selected for total transcriptome analysis (ongoing). Results: Immunohistochemical analysis demonstrated significant differences in the expression of 12 proteins, including CK7/20, in particular, oncofetal proteins such as SALL4 and Glypican 3 in JIAC compared to CRAC (15/52 vs. 3/190; P < 0.01). TP53 and ARID2 mutations were frequently identified as driver mutations in JIAC. Phylogenetic analysis revealed that JIAC exhibits a “long trunk – short branches” pattern, along with a higher peak in variant allele frequency distributions, suggesting stronger or more continuous selective pressure. Transcriptomic analysis revealed significant upregulation of CD24 , involved in cancer stem cell, and less frequency of WNT-signaling activation in JIAC. In addition, deconvolution analysis demonstrated a significant increase in helper T cells. Conclusions: These findings provide new insights into JIAC carcinogenesis and suggest the presence of a unique tumor microenvironment in the jejunoileum.
Ishikawa et al. (Sat,) studied this question.