De novo programmed cell death in oral cancer.
OBJECTIVE
The importance of programmed cell death or apoptosis in the maintenance of tissue homoeostasis and the pathogenesis of oral cancer was analysed in relation to apoptosis regulatory proteins, tissue proliferation and tumour histology.


RESULTS
The extent of apoptosis was defined by morphological criteria and the TUNEL (terminal deoxy nucleotidyl transferase-mediated dUTP biotin nick end labelling) assay. p53, bax, bcl-2 and cyclin D1 expression was evaluated by immunocytochemistry. The presence of mutant p53 was analysed using a mutant p53-specific ELISA. An inverse correlation was observed between TUNEL reactivity and histology of the lesion (r = -0.555, P = 0.0001). There was also correlation between TUNEL reactivity and immunoreactivity of apoptosis regulatory proteins. p53 (r = 0.641, P = 0.00023), bcl-2 (r = -0.642, P = 0.00014) and bax (r = 0.651, P = 0.00002). The presence of mutant p53 protein showed an inverse correlation to the extent of apoptosis (r = - 0.301, P = 0.00063). Significant correlation was evident between the bax/bcl-2 ratio and TUNEL (r = 0.652, P = 0.00001) as well as between cyclin D1 and TUNEL reactivity (r = 0.577, P = 0.00001).


CONCLUSIONS
Results from this study suggest that apoptosis decreases as histological abnormality increases. Apoptotic regulatory proteins are also altered in a histologically dependent manner. Deregulated proliferation occurs simultaneously with decreased apoptosis during tumour progression in the oral mucosa.
Ravi
D
D
Division of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala State, India.
Ramadas
K
K
Mathew
B S
BS
Nalinakumari
K R
KR
Nair
M K
MK
Pillai
M R
MR
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000473:pathology*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1