A study of TRAIL receptors in squamous cell carcinoma of the head and neck.
OBJECTIVE
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.


METHODS
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).


METHODS
The expression of TRAIL-R1 and TRAIL-R2 and the presence of the TRAIL-R1 polymorphisms C626G and G422A.


RESULTS
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).


CONCLUSIONS
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.
Teng
Marita S
MS
Department of Otolaryngology, University of Washington, Seattle, WA, USA.
Brandwein-Gensler
Margaret S
MS
Teixeira
Miriam S
MS
Martignetti
John A
JA
Duffey
Dianne C
DC
D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D004273:DNA, Neoplasm / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011110:Polymorphism, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha