Cell cycle regulating mechanisms in oral lichen planus: molecular bases in epithelium predisposed to malignant transformation.
OBJECTIVE
Expression of p53, p21, ki-67, Bcl-2 and caspase-3 proteins in oral lichen planus (OLP) was studied to investigate cell cycle regulation mechanisms in this disease.


METHODS
Oral biopsies were obtained from 51 patients with OLP and 26 controls for immunohistochemical analysis (peroxidase antiperoxidase) to quantify expression of the proteins under study (-: 0%, +: <10%, ++: 10-25%, +++: 26-50%, ++++: >50% positive cells).


RESULTS
Basal expression of caspase-3 was negative in 22 cases (46.8%) and positive in <10% of basal cells in 22 cases (46.8%); caspase-3 expression in inflammatory infiltrate was negative in 22 cases (46.8%) and positive in <10% of lymphocytes in 20 cases (42.5%). Basal expression of Bcl-2 was negative in 35 cases (74.5%); Bcl-2 was expressed in inflammatory infiltrate in 34 cases (72.3%) and was positive in <25% of lymphocytes in 14 of these (29.7%). Basal expression of p53 and p21 was positive in 32 (67.9%) and 23 (48.8%) cases, respectively. Basal expression of ki-67 was positive in 45 cases (95.7%), of which 20 (42.5%) showed positivity in >25% of cells; ki-67 was expressed in inflammatory infiltrate in 23 cases (48.9%). Significant associations were found between basal expressions of p53 and ki-67 (p<0.001) and between Bcl-2 expression in infiltrate and basal expression of ki-67 (p<0.001). No association was observed between basal expressions of p53 and caspase-3 (p=0.08). Bcl-2 expression in infiltrate and basal expression of ki-67 were independently associated with presence of OLP.


CONCLUSIONS
Epithelial cells in OLP do not preferentially develop apoptosis but rather cycle arrest or an increased proliferation rate, which may create a suitable substrate for malignant transformation.
González-Moles
M A
MA
School of Dentistry, Granada University, Paseo de Cartuja s/n, 18071 Granada, Spain. magonzal@ugr.es
Bascones-Ilundain
C
C
Gil Montoya
J A
JA
Ruiz-Avila
I
I
Delgado-Rodríguez
M
M
Bascones-Martínez
A
A
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000032:analysis; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000737:chemistry*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D017676:Lichen Planus, Oral / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3