Cho Tomonari, Shiozawa Eisuke, Urushibara Fumihiko, Arai Nana, Funaki Toshitaka, Takehara Yusuke, Tazawa Sakiko, Misawa Masashi, Homma Mayumi, Norose Tomoko, Omatsu Mutsuko, Miyachi Hideyuki, Yamochi Toshiko, Kunimura Toshiaki, Tate Genshu, Ishida Fumio, Kudo Shin-Ei, Takimoto Masahumi
Department of Pathology and Laboratory Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
Digestive Disease Center, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan.
Oncol Lett. 2017 Jun;13(6):4327-4333. doi: 10.3892/ol.2017.5959. Epub 2017 Mar 31.
Angiogenesis is essential for tumor growth and metastasis. CD105 is reportedly a specific marker for tumor angiogenesis. It has been demonstrated that monoclonal antibodies to CD105 have high affinity for activated endothelial cells. A relationship between metastasis and microvessel density (MVD), as an indicator of neovascularization, has been identified in patients with colorectal cancer as shown by the presence of monoclonal antibodies to CD105. However, data on potentially confounding factors such as lymphatic and vascular infiltration and tumor size are lacking. We further investigated the relationship between MVD and distant metastasis, along with potentially confounding clinicopathological factors, to more precisely characterize this relationship. In this retrospective study, we analyzed colorectal cancer specimens surgically or endoscopically resected from January to September 2009. We defined MVD as the number of microvessels stained by monoclonal antibodies to CD105 per ×400 field. Selected clinicopathological factors were analyzed and stepwise multivariate logistic regression was performed to identify independent risk factors for distant metastasis. We analyzed 129 lesions. The median follow-up time was 34 months (range, 6-85 months) in patients with distant metastasis and 61 months (range, 60-86 months) in those without distant metastasis. At the time of resection or during subsequent follow-up, 32 patients had distant metastases. The MVD was significantly greater in patients with than without distant metastases (mean ± standard deviation: 10.4±4.9 vs. 7.6±3.3, P=0.008; Welch's t-test). Stepwise multivariate logistic regression indicated that MVD, regional lymph node metastasis, and tumor size were independent risk factors for distant metastases. Combining assessment of monoclonal antibodies to CD105-positive MVD with assessment of regional lymph node metastasis and tumor size may help to identify patients who need more intensive surveillance after surgery for colorectal cancer.
血管生成对于肿瘤的生长和转移至关重要。据报道，CD105是肿瘤血管生成的特异性标志物。已经证明，针对CD105的单克隆抗体对活化的内皮细胞具有高亲和力。正如针对CD105的单克隆抗体所显示的那样，在结直肠癌患者中已确定转移与作为新生血管形成指标的微血管密度（MVD）之间存在关联。然而，缺乏关于潜在混杂因素如淋巴管和血管浸润以及肿瘤大小的数据。我们进一步研究了MVD与远处转移之间的关系，以及潜在的混杂临床病理因素，以更精确地表征这种关系。在这项回顾性研究中，我们分析了2009年1月至9月通过手术或内镜切除的结直肠癌标本。我们将MVD定义为每400倍视野中被针对CD105的单克隆抗体染色的微血管数量。分析选定的临床病理因素，并进行逐步多变量逻辑回归以确定远处转移的独立危险因素。我们分析了129个病变。远处转移患者的中位随访时间为34个月（范围6 - 85个月），无远处转移患者的中位随访时间为61个月（范围60 - 86个月）。在切除时或随后的随访期间，32例患者发生远处转移。发生远处转移的患者的MVD显著高于未发生远处转移的患者（平均值±标准差：10.4±4.9对7.6±3.3，P = 0.008； Welch t检验）。逐步多变量逻辑回归表明，MVD、区域淋巴结转移和肿瘤大小是远处转移的独立危险因素。将针对CD105阳性MVD的单克隆抗体评估与区域淋巴结转移和肿瘤大小评估相结合，可能有助于识别结直肠癌手术后需要更密切监测的患者。
