Kumagai Youichi, Tachikawa Tetsuhiko, Higashi Morihiro, Sobajima Jun, Takahashi Akemi, Amano Kunihiko, Fukuchi Minoru, Ishibashi Kei-Ichiro, Mochiki Erito, Yakabi Koji, Tamaru Jun-Ichi, Ishida Hideyuki
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
Esophagus. 2018 Jan;15(1):19-26. doi: 10.1007/s10388-017-0588-2. Epub 2017 Jul 24.
The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.
Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.
On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.
TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.
食管鳞状细胞癌早期胸苷磷酸化酶(TP)与血管生成之间的关系尚不清楚。
使用14份正常鳞状上皮样本、11份低级别上皮内瘤变样本和64份浅表食管癌样本,通过对CD34和CD105进行免疫染色来估计微血管密度(MVD)。还对癌细胞和基质单核细胞(SMC)中的TP表达进行了评估。然后我们研究了癌细胞和SMC中MVD与TP表达之间的相关性。
基于上述参数,癌性病变中的MVD显著高于正常鳞状上皮。就CD34和CD105表达而言,MVD从正常鳞状上皮到低级别上皮内瘤变,再到M1和M2期癌以及M3期或更深层癌呈现逐渐增加的趋势。M1和M2期癌在癌细胞和SMC中均显示TP过表达。癌细胞中的TP表达与根据CD34(rS = 0.16,P = 0.21)或CD105(rS = 0.05,P = 0.68)表达估计的MVD之间无显著相关性。SMC中的TP表达与CD34相关(rS = 0.46,P < 0.001)和CD105相关(rS = 0.34,P < 0.01)的MVD之间存在显著相关性。在M3期或更深层癌中,癌细胞或SMC中的TP表达与静脉侵犯、淋巴侵犯及淋巴结转移之间无显著相关性。
在食管鳞状细胞癌进展的极早期,癌细胞和基质单核细胞中的TP表达均被激活。SMC中的TP表达而非癌细胞中的TP表达与血管生成显著相关。