Teng Marita S, Brandwein-Gensler Margaret S, Teixeira Miriam S, Martignetti John A, Duffey Dianne C
Department of Otolaryngology, University of Washington, Seattle, WA, USA.
Arch Otolaryngol Head Neck Surg. 2005 May;131(5):407-12. doi: 10.1001/archotol.131.5.407.
To determine the potential immediate applicability of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2, the apoptotic forms of TRAIL-Rs, for preclinical testing.
Head and neck squamous cell carcinoma (HNSCC) tumors were studied for TRAIL-R1 and TRAIL-R2 expression by immunohistochemical analysis. In addition, matched tumor and peripheral blood DNA samples were screened for 2 known TRAIL-R1 coding single nucleotide polymorphisms (C626G and G422A). Subjects Tumor samples taken from 43 patients (37 samples for immunohistochemical analysis and 6 additional ones included for polymorphism analysis).
The expression of TRAIL-R1 and TRAIL-R2 and the presence of the TRAIL-R1 polymorphisms C626G and G422A.
Fewer than 25% of HNSCC tumor cells expressed TRAIL-R1 and TRAIL-R2. Surrounding tumor-infiltrating polymorphonuclear cells expressed TRAIL-R1 and TRAIL-R2 in 12 (32%) and 14 (38%) of cases, respectively. The TRAIL-R1 polymorphisms C626G and G422A were present in 36 (88%) and 33 (89%) cancer cases, respectively. Compared with control groups from another study, these polymorphism frequencies were statistically significant (P = .01 and .003, respectively).
TRAIL-R expression was detected in less than half of the tumor specimens studied but not in any surrounding normal tissue and was found in a higher frequency on tumor-infiltrating polymorphonuclear cells than on tumor cells. These findings support the idea that the presence of TRAIL-Rs on some HNSCC tumors may make them more susceptible to apoptosis, and they also suggest that TRAIL-R-associated mechanisms may result in immune-modulatory effects on tumor-infiltrating polymorphonuclear cells. Furthermore, the significant association of somatic TRAIL-R1 genetic polymorphisms in this sample of patients with HNSCC suggests a potential association between constitutive TRAIL-R1 polymorphisms and development of HNSCC. Defining TRAIL-R expression and genetic polymorphisms in HNSCC represents the first step in examining TRAIL-related mechanisms for their potential as therapeutic targets.
确定肿瘤坏死因子相关凋亡诱导配体受体1(TRAIL-R1)和TRAIL-R2(TRAIL-Rs的凋亡形式)在临床前测试中的潜在即时适用性。
通过免疫组织化学分析研究头颈部鳞状细胞癌(HNSCC)肿瘤中TRAIL-R1和TRAIL-R2的表达。此外,对匹配的肿瘤和外周血DNA样本进行筛查,以检测2种已知的TRAIL-R1编码单核苷酸多态性(C626G和G422A)。研究对象为取自43例患者的肿瘤样本(37份用于免疫组织化学分析,另外6份用于多态性分析)。
TRAIL-R1和TRAIL-R2的表达以及TRAIL-R1多态性C626G和G422A的存在情况。
少于25%的HNSCC肿瘤细胞表达TRAIL-R1和TRAIL-R2。在12例(32%)和14例(38%)病例中,周围肿瘤浸润的多形核细胞分别表达TRAIL-R1和TRAIL-R2。TRAIL-R1多态性C626G和G422A分别存在于36例(88%)和33例(89%)癌症病例中。与另一项研究的对照组相比,这些多态性频率具有统计学意义(P值分别为0.01和0.003)。
在所研究的肿瘤标本中,不到一半检测到TRAIL-R表达,但周围正常组织中未检测到,且在肿瘤浸润的多形核细胞上的出现频率高于肿瘤细胞。这些发现支持以下观点:某些HNSCC肿瘤上TRAIL-R的存在可能使其更易发生凋亡,并且还表明TRAIL-R相关机制可能对肿瘤浸润的多形核细胞产生免疫调节作用。此外,该HNSCC患者样本中体细胞TRAIL-R1基因多态性的显著关联表明,组成性TRAIL-R1多态性与HNSCC的发生之间可能存在关联。确定HNSCC中TRAIL-R的表达和基因多态性是研究TRAIL相关机制作为治疗靶点潜力的第一步。