Koide Naohiko, Nishio Akihito, Sato Toshiyuki, Sugiyama Atsushi, Miyagawa Shin-ichi
Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Am J Gastroenterol. 2004 Sep;99(9):1667-74. doi: 10.1111/j.1572-0241.2004.30733.x.
Macrophage chemoattractant protein-1 (MCP-1) is a chemokine-inducing infiltration of macrophages, which can play several roles in tumor growth and metastasis. We have attempted to clarify the relationship between MCP-1 expression and macrophage infiltration in esophageal squamous cell carcinoma (SCC).
Paraffin-embedded sections of tissue samples taken from 56 patients with esophageal SCC after curative surgery were immunohistochemically stained for MCP-1, CC chemokine receptor 2 (CCR-2), and thymidine phosphorylase (TP). Macrophage recruitment in SCC was evaluated by monocytic count based on CD68 immunostaining. Microvessels immunostained for Factor VIII-related antigen were counted in SCC, and microvessel density (MVD) was determined. Ki-67 labeling index was calculated based on Ki-67 immunostaining, and an apoptotic index was calculated based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling.
MCP-1 was expressed in cancer cells of 31 SCC (55.4%) and in stromal cells mainly identified as macrophages of 16 SCC (28.6%). CCR-2 was expressed in stromal cells of all SCC and in vascular endothelial cells of 15 SCC (26.8%). There was a significant correlation between the expression of MCP-1 in cancer cells and of CCR-2 in stromal cells. TP was expressed in stromal cells in 76.7% of the SCC. Monocytic count, MVD, and Ki-67 LI in SCC with MCP-1 expression in cancer cells were higher than that without, and apoptotic index in SCC with MCP-1 expression in cancer cells were lower than that without. Furthermore, the monocytic count was positively correlated with MVD, while it was inversely correlated with apoptotic index. Clinicopathologically, MCP-1 expression in cancer cells was correlated with venous invasion, distant metastasis, and lymph node metastasis. Monocytic count in SCC with venous invasion, distant metastasis, or lymph node metastasis was higher than that without them. Five-year survival rate in the patients with high monocytic count or MCP-1 expression was worse than that with a low monocytic count or without MCP-1 expression.
These results suggest that MCP-1 expression and macrophage infiltration is associated with angiogenic promotion in esophageal SCC. MCP-1 expression may be interactively associated with macrophage infiltration in esophageal SCC; MCP-1 may play an important role in tumor angiogenesis through production of angiogenic factors, such as TP, by recruited macrophages in esophageal SCC. Furthermore, CCR-2 expression in vascular endothelial cells may participate partially in angiogenesis. Clinicopathologically, esophageal SCC patients with MCP-1 expression have no favorable prognosis.
巨噬细胞趋化蛋白-1（MCP-1）是一种诱导巨噬细胞浸润的趋化因子，在肿瘤生长和转移中可发挥多种作用。我们试图阐明食管鳞状细胞癌（SCC）中MCP-1表达与巨噬细胞浸润之间的关系。
对56例接受根治性手术后的食管SCC患者的组织样本石蜡包埋切片进行免疫组织化学染色，检测MCP-1、CC趋化因子受体2（CCR-2）和胸苷磷酸化酶（TP）。基于CD68免疫染色通过单核细胞计数评估SCC中的巨噬细胞募集情况。对SCC中免疫染色为VIII因子相关抗原的微血管进行计数，并确定微血管密度（MVD）。基于Ki-67免疫染色计算Ki-67标记指数，并基于末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记计算凋亡指数。
MCP-1在31例SCC（55.4%）癌细胞中表达，在16例SCC（28.6%）主要鉴定为巨噬细胞的基质细胞中表达。CCR-2在所有SCC的基质细胞以及15例SCC（26.8%）的血管内皮细胞中表达。癌细胞中MCP-1的表达与基质细胞中CCR-2的表达之间存在显著相关性。TP在76.7%的SCC基质细胞中表达。癌细胞中表达MCP-1的SCC中的单核细胞计数、MVD和Ki-67标记指数高于未表达的，而癌细胞中表达MCP-1的SCC中的凋亡指数低于未表达的。此外，单核细胞计数与MVD呈正相关，而与凋亡指数呈负相关。在临床病理方面，癌细胞中MCP-1的表达与静脉侵犯、远处转移和淋巴结转移相关。有静脉侵犯、远处转移或淋巴结转移的SCC中的单核细胞计数高于无这些情况的。单核细胞计数高或MCP-1表达高的患者的5年生存率低于单核细胞计数低或无MCP-1表达的患者。
这些结果表明，MCP-1表达和巨噬细胞浸润与食管SCC中的血管生成促进有关。MCP-1表达可能与食管SCC中的巨噬细胞浸润相互关联；MCP-1可能通过食管SCC中募集的巨噬细胞产生血管生成因子（如TP）在肿瘤血管生成中发挥重要作用。此外，血管内皮细胞中CCR-2的表达可能部分参与血管生成。在临床病理方面，有MCP-1表达的食管SCC患者预后不佳。
