Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Lung Cancer. 2010 Oct;70(1):88-93. doi: 10.1016/j.lungcan.2009.12.014. Epub 2010 Jan 12.
A monoclonal antibody D2-40 has been widely used for tumor lymphangiogenesis and lymphatic vessel invasion (LVI) in human cancers. However, the clinical significance of the tumor cell D2-40 immunoreactivity has not been clearly understood.
We evaluated the tumor cell D2-40 immunoreactivity in non-small cell lung cancer (NSCLC). One hundred and forty-seven NSCLC patients were investigated. Immunohistochemistry using D2-40 was performed to evaluate the tumor cell D2-40 immunoreactivity, micro-lymphatic vessel density (Micro-LVD) and LVI. The intratumoral microvessels density (MVD) was evaluated by the CD34-immunostaining, and tumor proliferation was evaluated by the Ki-67-immunostaining.
The percentage of D2-40-positive tumor cells was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001), and all D2-40-strong tumors were squamous cell carcinomas. The percentage of D2-40-strong tumors was significantly higher in moderately to poorly differentiated tumors than in well-differentiated tumors (P=0.0332). Furthermore, the Ki-67 proliferation index in D2-40-strong tumors was significantly the highest. However, the tumor cell D2-40 immunoreactivity was not associated with Micro-LVD, LVI, or MVD. Regarding the patient survival, the overall survival was significantly lower in patients with D2-40-strong tumors than in patients with D2-40-negative or D2-40-weak tumors (P=0.0005). Multivariate analyses also revealed the tumor cell D2-40 immunoreactivity to be a significant prognostic factor of poor prognosis for NSCLC patients (P=0.0007).
The D2-40 immunostaining is useful to identify aggressive squamous cell carcinomas of the lung.
单克隆抗体 D2-40 已被广泛用于人类癌症的肿瘤淋巴管生成和淋巴管侵犯(LVI)。然而,肿瘤细胞 D2-40 免疫反应的临床意义尚不清楚。
我们评估了非小细胞肺癌(NSCLC)中的肿瘤细胞 D2-40 免疫反应性。对 147 名 NSCLC 患者进行了研究。使用 D2-40 进行免疫组织化学染色,以评估肿瘤细胞 D2-40 免疫反应性、微淋巴管密度(Micro-LVD)和 LVI。肿瘤内微血管密度(MVD)通过 CD34 免疫染色评估,肿瘤增殖通过 Ki-67 免疫染色评估。
D2-40 阳性肿瘤细胞的百分比在鳞状细胞癌中明显高于腺癌(P<0.0001),所有 D2-40 强肿瘤均为鳞状细胞癌。D2-40 强肿瘤的百分比在中至低分化肿瘤中明显高于高分化肿瘤(P=0.0332)。此外,D2-40 强肿瘤的 Ki-67 增殖指数明显最高。然而,肿瘤细胞 D2-40 免疫反应性与 Micro-LVD、LVI 或 MVD 无关。关于患者生存,D2-40 强肿瘤患者的总生存率明显低于 D2-40 阴性或 D2-40 弱阳性肿瘤患者(P=0.0005)。多变量分析还显示,肿瘤细胞 D2-40 免疫反应性是 NSCLC 患者预后不良的显著预后因素(P=0.0007)。
D2-40 免疫染色有助于识别侵袭性肺鳞状细胞癌。