Role of p53 and bcl2 as markers of vitamin A response in premalignant lesions of the oral cavity.

Oral cancer accounts for 40 to 50% of cancers diagnosed in India. Oral cancer is preceeded in most cases by pre malignant lesions-leukoplakia, submucous fibrosis and lichen planus. Stoppage of causative agents reverts premalignant lesions in some of the cases only. Thus anti oxidant therapy is being used to revert premalignant change to normal. Few studies available, have taken clinical parameters as indicators of response to therapy. Extensive medline search failed to reveal any study at the cellular level. This study attempts to investigate for the first time the role of p53 and bcl2 as markers of prognosis following vitamin A therapy. 24 cases of pre malignant lesions of oral cavity were studied. 1 lakh IU of vitamin A were given orally twice a week for 3 months. Biopsies were done before and after therapy. Haematoxylin and Eosin stain was done to confirm diagnosis. Immunostaining for mutant p53 and bcl2 was done on paraffin sections. 500 cells were counted over an average of 5 HPF and percentage positivity was calculated. Statistical analysis was done by applying the paired t tests. In 19 cases (79.2%) of premalignant lesions mutant p53 expression was zero before therapy, and remained unchanged even after the therapy. 3 cases (12.5%) had high mutant p53 values which reduced following therapy (p = 0.037). Therapy thus proved effective in these cases. However, in 2 cases (8.3%) pre therapy values of zero showed an increase after vitamin A therapy. These were the cases which had dysplasia and were chronic smokers. In 2 cases (8.3%) pre therapy values of bcl2 were zero and remained unchanged even after therapy and these cases did not stop smoking even during the vitamin A therapy. In 12 cases (50.0%) higher pre therapy values were reduced after therapy (p < 0.0001). Vitamin A therapy was effective in these cases. However, in 10 cases (42.0%) expression of bcl2 increased subsequent to therapy. Therapy failed in these cases because of chronic heavy smoking and tobacco chewing. Thus, in the majority of cases vitamin A was effective in preventing mutation of p53 (91.7%) and expression of bcl2 (58.0%). In effect, these two oncoproteins can be used as prognostic markers and follow up for anti oxidant therapy.