Expression of the
hyaluronan-mediated motility receptor (RHAMM, CD168) predicts adverse clinicopathological features and decreased survival for
colorectal cancer (CRC) patients. Using full tissue sections, we investigated the expression of RHAMM in
tumor budding cells of 103 primary
CRCs to characterize the biological processes driving single-cell invasion and early metastatic dissemination. RHAMM expression in
tumor buds was analyzed with clinicopathological data, molecular features and survival.
Tumor budding cells at the invasive front of CRC expressed RHAMM in 68% of cases. Detection of RHAMM-positive
tumor budding cells was significantly associated with poor survival outcome (P = .0312), independent of TNM stage and adjuvant
therapy in multivariate analysis (P = .0201). RHAMM-positive
tumor buds were associated with frequent lymphatic invasion (P = .0007), higher
tumor grade (P = .0296), and nodal
metastasis (P = .0364). Importantly, the prognostic impact of RHAMM expression in
tumor buds was maintained independently of the number of
tumor buds found in an individual case (P = .0246). No impact of KRAS/BRAF mutation,
mismatch repair deficiency and CpG island methylation was observed. RHAMM expression identifies an aggressive subpopulation of
tumor budding cells and is an independent adverse prognostic factor for CRC patients. These data support ongoing efforts to develop RHAMM as a target for precision
therapy.