Alterations of p53, cyclin D1, Rb, and H-ras in human oral carcinomas related to tobacco use.
BACKGROUND
Epidemiologic studies have indicated that environmental and personal habits, particularly tobacco use and alcohol abuse, are major etiologic factors in the induction and progression of head and neck squamous cell carcinomas (HNSCC). Molecular studies have focused on HNSCC related to smoking but not those associated with smokeless tobacco.


METHODS
The authors studied immunohistochemical evidence of alterations of p53, cyclin D1, and Rb in 34 human oral carcinomas related to tobacco use. They also examined p53 and H-ras using single strand conformation polymorphism (SSCP) and sequencing analysis.


RESULTS
Overexpression of cyclin D1 was found in 41% of cases, and accumulation of p53 was found in 59%. Only 9% of the samples did not show Rb staining. In SSCP and sequencing analysis, 17 cases showed mutations in the conserved region of the p53 gene. No mutations were detected in codons 12, 13, or 61 of the H-ras gene.


CONCLUSIONS
Overexpression of cyclin D1 and p53 mutations are common alterations in HNSCC. In contrast, the loss of Rb function seems to occur infrequently, and mutations in the H-ras gene apparently do not play a role in this cancer. HNSCC associated with smokeless tobacco contained the same alterations as those related to smoking.
The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
J
J
Xu
I B
IB
Gimenez-Conti
J E
JE
Cunningham
A M
AM
Collet
M A
MA
Luna
H E
HE
Lanfranchi
M R
MR
Spitz
C J
CJ
Conti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D019940:Genes, bcl-1 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D010947:Plants, Toxic; D016160:Retinoblastoma Protein / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D014030:Tobacco, Smokeless / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53