TY - JOUR
T1 - Nitric oxide and apoptosis during human head and neck squamous cell carcinoma development
AU - Bentz, Brandon G.
AU - Chandra, Rakesh
AU - Haines, G. Kenneth
AU - Robinson, Alan M.
AU - Shah, Pinky
AU - Radosevich, James A.
PY - 2002
Y1 - 2002
N2 - Purpose: Apoptosis index (AI), Bcl-2, and Bax have shown prognostic significance in head and neck squamous cell carcinoma (HNSCCa). Other areas of research have implicated nitric oxide (NO) or its various intermediate species in both proapoptotic and antiapoptotic processes. We have previously shown that NO-generating enzymes are significantly increased during the stepwise progression to HNSCCa. The aim of this study was to explore the interrelationship of NO and a known consequence of NO-related oxidative stress, apoptosis, during this step-wise process. Materials and Methods: Formalin fixed-paraffin embedded tissue samples of 10 normal oral mucosa, 15 reactive/dysplastic lesions, and 17 HNSCCa lesions studied previously were subjected to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP labeling (TUNEL) assay as well as immunohistochemical staining against Bcl-2, Bax, and p53. Patient charts were reviewed and clinical data were compared. The study pathologist (G.K.H) reviewed these slides blinded to patient identifiers or clinical data. The number of immunopositive cell nuclei or staining intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with the results of immunostaining previously obtained for endothelial constitutive NO synthase (ecNOS) and nitrotyrosine. Results: Compared with normal oral mucosa, the Al, Bcl-2, Bax, Bcl-2/Bax intensity and frequency ratios, and mutant p53 intensity significantly changed in reactive/dysplastic and HNSCCa lesions (P < .001 for all). Correlations between the staining characteristics of the antigens studied are presented. Furthermore, perilesional inflammatory cells showed staining in the TUNEL assay. Conclusions: In a set of tissue samples previously well characterized, these new findings implicate a link between NO and the induction of apoptotic cell death in HNSCCa development.
AB - Purpose: Apoptosis index (AI), Bcl-2, and Bax have shown prognostic significance in head and neck squamous cell carcinoma (HNSCCa). Other areas of research have implicated nitric oxide (NO) or its various intermediate species in both proapoptotic and antiapoptotic processes. We have previously shown that NO-generating enzymes are significantly increased during the stepwise progression to HNSCCa. The aim of this study was to explore the interrelationship of NO and a known consequence of NO-related oxidative stress, apoptosis, during this step-wise process. Materials and Methods: Formalin fixed-paraffin embedded tissue samples of 10 normal oral mucosa, 15 reactive/dysplastic lesions, and 17 HNSCCa lesions studied previously were subjected to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP labeling (TUNEL) assay as well as immunohistochemical staining against Bcl-2, Bax, and p53. Patient charts were reviewed and clinical data were compared. The study pathologist (G.K.H) reviewed these slides blinded to patient identifiers or clinical data. The number of immunopositive cell nuclei or staining intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with the results of immunostaining previously obtained for endothelial constitutive NO synthase (ecNOS) and nitrotyrosine. Results: Compared with normal oral mucosa, the Al, Bcl-2, Bax, Bcl-2/Bax intensity and frequency ratios, and mutant p53 intensity significantly changed in reactive/dysplastic and HNSCCa lesions (P < .001 for all). Correlations between the staining characteristics of the antigens studied are presented. Furthermore, perilesional inflammatory cells showed staining in the TUNEL assay. Conclusions: In a set of tissue samples previously well characterized, these new findings implicate a link between NO and the induction of apoptotic cell death in HNSCCa development.
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U2 - 10.1053/ajot.2002.28772
DO - 10.1053/ajot.2002.28772
M3 - Article
C2 - 11791242
AN - SCOPUS:0036145793
SN - 0196-0709
VL - 23
SP - 4
EP - 11
JO - American Journal of Otolaryngology - Head and Neck Medicine and Surgery
JF - American Journal of Otolaryngology - Head and Neck Medicine and Surgery
IS - 1
ER -