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Expression of the hyaluronan-mediated motility receptor RHAMM in tumor budding cells identifies aggressive colorectal cancers.

Abstract
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.
AuthorsViktor Hendrik Koelzer, Bettina Huber, Valentina Mele, Giandomenica Iezzi, Mafalda Trippel, Eva Karamitopoulou, Inti Zlobec, Alessandro Lugli
JournalHuman pathology (Hum Pathol) Vol. 46 Issue 11 Pg. 1573-81 (Nov 2015) ISSN: 1532-8392 [Electronic] United States
PMID26351067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • Hyaluronan Receptors
  • hyaluronan-mediated motility receptor
Topics
  • Adenocarcinoma (metabolism, mortality, pathology)
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (metabolism)
  • Colorectal Neoplasms (metabolism, mortality, pathology)
  • Extracellular Matrix Proteins (metabolism)
  • Female
  • Humans
  • Hyaluronan Receptors (metabolism)
  • Intestinal Mucosa (metabolism, pathology)
  • Lymphatic Metastasis (pathology)
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Tissue Array Analysis

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