Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul St, Mary's Hospital, 222 Banpo-daero, Seocho-gu, 137-701 Seoul, Korea.
BMC Cancer. 2014 Feb 24;14:125. doi: 10.1186/1471-2407-14-125.
The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2).
Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2.
Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05).
Wnt3a and wnt5a expression had a concordance rate higher than 60% with a high concordance rate between the primary tumor and metastatic site. Wnt3a expression is associated with the expression of MMP-9 in primary tumor tissue adjacent mesenchymal tissue, and at the metastatic site. As a prognostic marker, only β-catenin expression showed significant relation with survival outcome.
已知 wnt/β-连环蛋白信号通路通过与肿瘤微环境相互作用，影响癌症的发生和进展。然而，wnt3a 和 wnt5a 在结直肠癌（CRC）中的作用尚未得到充分研究。在本研究中，我们研究了 CRC 中 wnt 蛋白的表达及其在原发性肿瘤和转移部位的一致性率。为了确定 wnt 蛋白与侵袭相关蛋白的关系，我们还分析了 wnt 蛋白表达与基质金属蛋白酶-9（MMP-9）和血管内皮生长因子受体-2（VEGFR-2）表达之间的相关性。
从 83 个石蜡包埋块中获得肿瘤组织，每个患者的原发性肿瘤和转移部位均使用切除的组织。我们对 wnt3a、wnt5a、β-连环蛋白、MMP-9 和 VEGFR-2 进行了免疫组织化学染色。
wnt3a、wnt5a、β-连环蛋白和 MMP-9 的表达较高；这些蛋白在超过 50%的原发性肿瘤中表达，但在转移部位的组织中表达较低。wnt5a 和 wnt3a、β-连环蛋白的原发性肿瘤和转移部位之间的一致性率分别为 76.2%和 79.4%，但 VEGFR-2 在转移部位的表达率为 67.4%，即使在原发性肿瘤中未发现。原发性肿瘤中 wnt3a 的表达与淋巴结受累显著相关（p=0.038），与原发性肿瘤中 MMP-9 的表达显著相关（p=0.0387），与肿瘤周围间质组织显著相关（p=0.022）和转移部位（p=0.004）。这些蛋白的表达之间没有其他关系。原发性肿瘤组织中的血管侵犯可能是肝转移的一个潜在预后标志物，但在 wnt 蛋白、MMP-9 和 VEGFR-2 之间没有观察到与腹膜种植的显著相关性。在生存分析中，β-连环蛋白的表达与总生存显著相关（p=0.05）。
wnt3a 和 wnt5a 的表达一致性率高于 60%，原发性肿瘤和转移部位之间的一致性率较高。wnt3a 的表达与原发性肿瘤组织周围间质组织和转移部位的 MMP-9 表达相关。作为预后标志物，只有β-连环蛋白的表达与生存结果有显著关系。
