Sanlioglu Ahter D, Korcum Aylin F, Pestereli Elif, Erdogan Gulgun, Karaveli Seyda, Savas Burhan, Griffith Thomas S, Sanlioglu Salih
Human Gene Therapy Unit, Akdeniz University Faculty of Medicine, Antalya, Turkey
Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):716-23. doi: 10.1016/j.ijrobp.2007.03.057. Epub 2007 May 18.
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration.
Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns.
The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions.
DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）可选择性诱导癌细胞凋亡，而对正常细胞无此作用。最近已启动多项临床试验，以测试TRAIL在癌症患者中的安全性和抗肿瘤潜力。已鉴定出四种不同的受体可与TRAIL相互作用：两种是死亡诱导受体（TRAIL-R1 [DR4]和TRAIL-R2 [DR5]），而另外两种（TRAIL-R3 [DcR1]和TRAIL-R4 [DcR2]）在结合后不会诱导死亡，并且被认为可抵消TRAIL诱导的细胞毒性。由于最近发现DcR2的高表达与前列腺癌和肺癌的发生相关，本研究在考虑各种预后标志物的情况下，调查了TRAIL和TRAIL受体表达在浸润性导管癌乳腺癌患者中的重要性。
使用TRAIL和TRAIL受体特异性抗体对90例浸润性导管癌乳腺癌患者进行免疫组织化学分析。分析了年龄、绝经状态、肿瘤大小、淋巴结状态、肿瘤分级、淋巴管浸润、神经周围浸润、肿瘤包膜外扩展、广泛导管内成分的存在、多中心性、雌激素和孕激素受体状态以及CerbB2表达水平与TRAIL/TRAIL受体表达模式的关系。
浸润性导管癌患者中表达最高的TRAIL受体是DR4。尽管孕激素受体阳性患者的DR5表达较低，但CerbB2阳性组织中DR5和TRAIL的表达水平均较高。
在浸润性导管癌乳腺癌患者中，DR4表达与肿瘤分级呈正相关。
