Surgical Oncology Laboratory, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska University Hospital/Östra, Sahlgrenska Academy at University of Gothenburg, SU Sahlgrenska, 41345, Gothenburg, Sweden.
Department of Microbiology and Immunology, University of Gothenburg, Medicinaregatan 7, 41390, Gothenburg, Sweden.
Clin Transl Oncol. 2022 Sep;24(9):1818-1827. doi: 10.1007/s12094-022-02839-2. Epub 2022 May 14.
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.
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.
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).
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.
肿瘤相关巨噬细胞（TAM）被认为有助于结直肠癌（CRC）的生长。在胸苷磷酸化酶（TYMP）表达的 CRC 中，巨噬细胞浸润程度高可能与预后不良相关。CD163 表达的预后影响，一种与 TAM 相关的受体，以及基质中 TYMP 的表达，分别在肿瘤组织中尚未确定。本研究的目的是确定 TYMP 和 CD163 表达水平与 II 期 CRC 患者无复发生存期（RFS）之间的潜在关联，并确定微切割是否重要。
对接受根治性切除且复发的 II 期 CRC 患者（n=104）进行匹配，以获得 5 年无复发生存随访的患者（n=206）。在冷冻肿瘤组织和分离为肿瘤上皮和基质的福尔马林固定肿瘤组织的微切割中分析 TYMP 和 CD163 的基因表达。
TYMP 表达在低分化肿瘤、右半结肠癌和高微卫星不稳定性肿瘤中较高，靠近肿瘤上皮细胞的 CD163 表达的巨噬细胞在低分化和 T4 肿瘤中高表达。肿瘤上皮细胞中 TYMP 表达高与无复发生存期较短相关（风险比 1.66；95%置信区间：1.09-2.56；p<0.05）。
肿瘤上皮细胞中 TYMP 的表达与 RFS 相关，强调了组织微切割的必要性。需要进一步研究以确定 TYMP 和 CD163 是否可以提供临床相关信息，以识别可能受益于辅助化疗的高危 II 期患者。
