Relationship between molecular markers and treatment response in a retrospective cohort of Indian patients with primary carcinoma of the larynx R. Sahoo a , V. Chittibabu a , G. Patil a , S. Rao a , S. Thakur a , G. Dhondalay a , A.J. Kulkarni a , A. Banerjee a , B.S. Ajaikumar b , A. Korlimarla a , A. Nargund a , R.N. Niti b , K.S. Gopinath b , Shilpa Prabhudesai a , R.M. Raghavendra a,b, * a Triesta Sciences (India) Pv Ltd., No. 8, Kalinga Rao Rd., Sampangiramanagar, Bangalore 560027, India b HCG Foundation, No. 8, P. Kalinga Rao Rd., Sampangiramanagar, Bangalore 560027, India article info Article history: Received 12 June 2009 Received in revised form 16 July 2009 Accepted 16 July 2009 Available online xxxx Keywords: p53 Mutation Carcinoma of the larynx Treatment response Prognostic markers Cisplatin resistance Larynx preservation summary 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 resis- tance in carcinoma of the larynx patients. In this study, we evaluate the relationships between p53 over expression/mutations, bcl 2 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 bcl 2 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 bcl 2 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 bcl 2 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. Ó 2009 Elsevier Ltd. All rights reserved. Background Head and neck cancers constitute a large proportion of cancers in India accounting for 23% of all cancers in males and 6% of all can- cers in females. 1 Majority of these cancers are preventable and are related to consumption of tobacco, alcohol, poor hygiene, diet and viral infections. 2 carcinoma of the larynx and preferably, squamous cell carcinoma constitutes 78% of all head and neck malignancies. The average 5-year survival for head and neck cancer ranges between 20% and 90% depending on the site and extent of the disease. 3 The preferred surgical treatment for advanced laryngeal tumors remains total laryngectomy (TL), a surgical technique in which lar- yngeal speech is sacrificed. However, of late radiation and chemo- therapy, along with subtotal laryngectomies that form a part of the so-called organ sparing protocols have also resulted in effective outcomes in western populations. 4 In India most of these cancers present at an advanced stage (stage III and above) thus pitting the principles of oncologically sound resection against organ pres- ervation. Currently used organ sparing protocols such as cisplatin analogues and radiotherapy that are used in the treatment of head and neck cancers are not always effective in tumor killing due to development of resistance. 5 Cisplatin forms adduct in DNA and is a mutagen in mammalian cells. 6–9 Current evidence suggests that cisplatin resistance arises through a combination of mutagenesis that generates highly cisplatin-resistant clones in the surviving population with 1368-8375/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2009.07.013 * Corresponding author. Address: Research Head, Investigator Initiated Trials, Triesta Sciences Pvt. Ltd., HCG Towers, No. 8, P. Kalinga Rao Road, Sampangira- managar, Bangalore 560027, India. Tel.: +91 80 40206122/9916488864; fax: +91 80 22485962. E-mail address: raghav.hcgrf@gmail.com (R.M. Raghavendra). Oral Oncology xxx (2009) xxx–xxx Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology ARTICLE IN PRESS Please cite this article in press as: Sahoo R et al. Relationship between molecular markers and treatment response in a retrospective cohort of Indian pa- tients with primary carcinoma of the larynx. Oral Oncol (2009), doi:10.1016/j.oraloncology.2009.07.013