Tumor-Associated Fusobacterium nucleatum and Aggressive Architectural Features in Stage II Colorectal Cancer.

Tumor budding (TB) and poorly differentiated clusters (PDCs) are histopathological indicators of invasive potential in colorectal cancer (CRC). Concurrently, Fusobacterium nucleatum (F. nucleatum) has emerged as a modulator of CRC progression. The relationship between intratumoral F. nucleatum and aggressive tumor architecture remains unknown. We evaluated 257 stage II primary CRCs. TB and PDC were assessed at the invasive front. Intratumoral F. nucleatum DNA was quantified from FFPE samples using droplet digital PCR. Associations between F. nucleatum load and molecular and clinicopathological features were analyzed. F. nucleatum was detected in 44.4% of tumors, with 19.8% classified as high bacterial load. Tumors with high F. nucleatum had a significantly higher frequency of intermediate- and high-grade PDCs (p = 0.047), with a specific enrichment for high-grade PDCs (p = 0.019). High F. nucleatum load was also associated with microsatellite instability (MSI-H). No significant associations were observed between F. nucleatum presence or load and 10-year overall, disease-free, and cancer-specific survival. A high F. nucleatum intratumoral burden was associated with aggressive tumor architecture characterized by PDC in stage II CRC. Nevertheless, no impact on long-term clinical outcomes was observed, indicating that F. nucleatum had limited prognostic value.