Glutathione S-transferase pi in squamous cell carcinoma of the head and neck.
OBJECTIVE
Oxidative/reductive (redox) DNA damage from radical species such as nitric oxide (NO*) are increasingly being implicated in the development of cancer. Moreover, redox-protective cellular mechanisms, such as glutathione S-transferase, may determine cellular susceptibility to this redox-mediated damage.


METHODS
Formalin-fixed, paraffin-embedded tissue samples of 11 normal oral mucosa, 15 reactive/dysplastic lesions, and 131 head and neck squamous cell carcinomas (HNSCCs) were immunohistochemically stained using a polyclonal antibody against glutathione S-transferase pi (GST-pi). Slides were reviewed in a blinded fashion by the study pathologist (G.K.H.) and intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with those obtained using monoclonal antibodies against endothelial constitutive nitric oxide synthase (ecNOS) and nitrotyrosine, a marker of NO*'s pathological nitrosylation of proteins on serial sections of the same tissue. Patient charts were reviewed and clinical data collected.


RESULTS
The expression of GST-pi was significantly increased in reactive/dysplastic and HNSCC samples compared with normal squamous mucosa (P < .001 for both). Furthermore, among the carcinomas the expression of GST-pi was significantly increased in higher-grade lesions (P < .02). The expression of GST-pi correlated highly with the expression of ecNOS and nitrotyrosine (P < .0001 for both).


CONCLUSIONS
These findings demonstrate that GST-pi is upregulated in conjunction with the NO*-generating ecNOS isoform and implicate GST-pi in protecting HNSCC from the cytotoxic effects of high concentrations of NO* found in the tumor bed.
Bentz
B G
BG
Department of Otolaryngology--Head and Neck Surgery, Northwestern University Medical Center, and Veterans Affairs Chicago Health Care Systems, Lakeside Hospital, Illinois 60611-3008, USA.
Haines
G K
GK
Radosevich
J A
JA
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis*; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D015854:Up-Regulation
D007527:Isoenzymes; C002744:3-nitrotyrosine; D014443:Tyrosine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase