Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin.
BACKGROUND
Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied.


METHODS
We immunohistochemically examined the expression of tumor-related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method.


RESULTS
Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible.


CONCLUSIONS
The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression.
Saito
K
K
Department of Preventive Dentistry, School of Dentistry, Tohoku University, Sendai, Japan.
Mori
S
S
Tanda
N
N
Sakamoto
S
S
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects; D014408:Biomarkers, Tumor; D002121:Calcium Channel Blockers / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000209:etiology / Q000378:metabolism; D002478:Cells, Cultured; D046508:Culture Techniques; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D005885:Gingival Hyperplasia / Q000139:chemically induced* / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D005887:Gingival Neoplasms / Q000737:chemistry / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
D000927:Anticonvulsants; D014408:Biomarkers, Tumor; D002121:Calcium Channel Blockers; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D010672:Phenytoin; D009543:Nifedipine