Relationship between molecular markers and treatment response in a retrospective cohort of Indian patients with primary carcinoma of the larynx

p53 Mutations and over expression have been shown to predict treatment response in head and neck cancer patients. Failure of organ sparing therapy has been attributed to cisplatin and radiotherapy resistance in carcinoma of the larynx patients. In this study, we evaluate the relationships between p53 over expression/mutations, bcl2 expression and ploidy status in a retrospective cohort of responder and non-responder carcinoma of the larynx patients.

Tissue samples from 22 patients with histopathologically confirmed carcinoma of the larynx and matched for age, stage, node status and treatment regimen, were analysed from our tissue biorepository. Differences in the above molecular markers were analysed between the responders and non-responders to conventional treatment. p53 and bcl2 over expression was checked by IHC and p53 mutation by PCR and direct sequencing. DNA ploidy and S-phase fractions were also analysed. Chi square analysis was used to identify changes in proportions of these markers in responders and non-responders and likelihood ratio test was done to determine the best predictor biological marker for treatment response. Bivariate relationships were determined between these variables using Spearman’s rank correlation.

Node negativity at time of diagnosis (p=0.05), p53 mutation (p=0.02) and bcl2 negativity (p=0.05) are some of the factors that are known to influence treatment response in our study. p53 over expression, S-phase fractions and ploidy status did not seem to influence treatment response. There was a significant inverse correlation between stage of cancer (p=0.03) and node positivity (p=0.06) with bcl2 positivity. There was an inverse correlation between mutation category to treatment response (p=0.01).

The results suggest p53 mutations to be a promising marker in predicting treatment response in carcinoma of the larynx patients.