Young patients with oral squamous cell carcinoma: study of the involvement of GSTP1 and deregulation of the Fanconi anemia genes.
OBJECTIVE
To investigate whether oral squamous cell carcinomas (OSCCs) from young (</=40 years) and older (>/=60 years) patients have differential expression levels of GSTP1, FANCA, FANCC, FANCD2, and FANCG.


METHODS
Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analysis were used to assess gene and protein expression, respectively.


METHODS
This study was performed in a research institute within a hospital setting.


METHODS
Our study group consisted of 104 patients (42 young and 62 older). We collected RNA from 32 OSCC samples (10 young and 22 older patients) for gene expression analysis. Seventy-seven OSCC samples (37 from young and 40 from older patients) were used for protein expression analysis. Five patients were studied in both analyses.


RESULTS
Lower expression of GSTP1 (P = .04) and FANCA (P = .01) was observed in the tumors of young compared with older patients. We also detected lower expression of GSTP1 in the tumors of young patients compared with their nondysplastic mucosa (P = .01). FANCA was underexpressed in nondysplastic mucosa of young compared with older patients (P = .01). GSTP1 protein showed negative or low expression in 41% (n = 15 of 37) of young vs 5% (n = 2 of 40) of older patient tumors (P = .001). FANCG protein expression was absent or low in 81% (n = 30 of 37) of young compared with 36% (n = 15 of 40) of older patient tumors (P<.001).


CONCLUSIONS
Differences in expression levels of GSTP1, FANCA, and FANCG in OSCC of young and older patients suggest that different mechanisms may be involved in tumor development through defective carcinogen metabolism and/or DNA repair capabilities. GSTP1 plays a key role in detoxification; therefore, underexpression of this gene in tumors of young patients may cause deficient detoxification that could lead to an increased susceptibility to the development of oral carcinoma.
Tremblay
Steve
S
Faculte de Medecine Dentaire, Universite Laval, Quebec City, Quebec.
Pintor Dos Reis
Patricia
P
Bradley
Grace
G
Galloni
Natalie Naranjo
NN
Perez-Ordonez
Bayardo
B
Freeman
Jeremy
J
Brown
Dale
D
Gilbert
Ralph
R
Gullane
Patrick
P
Irish
Jonathan
J
Kamel-Reid
Suzanne
S
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051856:Fanconi Anemia Complementation Group Proteins; D051549:Glutathione S-Transferase pi