4.4 Article

Impact of thymidine phosphorylase and CD163 expression on prognosis in stage II colorectal cancer

Journal

CLINICAL & TRANSLATIONAL ONCOLOGY
Volume 24, Issue 9, Pages 1818-1827

Publisher

SPRINGER INT PUBL AG
DOI: 10.1007/s12094-022-02839-2

Keywords

Macrophages; Thymidine phosphorylase; Colorectal neoplasm; Biomarkers; Microdissection; Microsatellite instability

Categories

Funding

  1. Swedish Cancer Society [CAN 2015/4999]
  2. Lions Cancer Research Foundation [LCV 2017
  3. 38]
  4. Assar Gabrielsson Foundation [FB15-51]
  5. Swedish Society of Medicine [SLS-689001]
  6. Goteborg Medical Society [GLS499861]
  7. Anna-Lisa and Bror Bjornsson Foundation
  8. University of Gothenburg
  9. Swedish state under the LUA/ALF agreement [ALFGBG-784211]

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This study found that high TYMP expression in tumor epithelial cells is associated with shorter relapse-free survival in stage II CRC patients. Tissue microdissection is important for accurate analysis. Further research is needed to explore the clinical relevance of TYMP and CD163 in identifying high-risk stage II patients who may benefit from adjuvant chemotherapy.
Background Tumor-associated macrophages (TAM) are known to facilitate colorectal cancer (CRC) growth. High macrophage infiltration in thymidine phosphorylase (TYMP) expressing CRC may correspond to poor prognosis. The prognostic impact of the expression CD163, a receptor associated with TAM, and TYMP in stroma, respectively, tumor tissue is not yet established. The aim of this study was to identify the potential associations between TYMP and CD163 expression levels and relapse-free survival (RFS) of patients with stage II CRC, and if microdissection is of importance. Methods Stage II CRC patients, radically resected with relapse (n = 104), were matched to patients with a 5-year relapse-free follow-up (n = 206). Gene expression of TYMP and CD163 was analyzed in snap-frozen tumor tissues and in microdissected formalin-fixed tumor tissues separated into tumor epithelium and stroma. Results TYMP expression was high in poorly differentiated tumors, right-sided CRC, and tumors with high microsatellite instability CD163-expressing macrophages near tumor epithelial cells had high expression in poorly differentiated and T4 tumors. High TYMP expression in tumor epithelial cells was in the multivariate analyses associated with shorter relapse-free survival (hazard ratio 1.66; 95% confidence interval: 1.09-2.56; p < 0.05). Conclusions TYMP expression in tumor epithelial cells was associated with RFS and emphasizes the need for tissue microdissection. Additional studies are needed to establish whether TYMP and CD163 could add clinically relevant information to identify high-risk stage II patients that could benefit from adjuvant chemotherapy.

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