

P53 & C-MYC ALTERATIONS IN CARCINOMA ORAL CAVITY & THEIR ROLE IN PREDICTING RESPONSE TO CHEMOTHERAPY
Abstract
Aims: (1) To study p53 alterations & its role in predicting response to neo-adjuvant chemotherapy in patients of carcinoma oral cavity. (2) To study c-myc expression & its role in predicting response to neo-adjuvant chemotherapy in patients of carcinoma oral cavity.
Methods and Material: Total of 30 patients with histologically proven squamous cell cancer of oral cavity having performance status of up to two according to the criteria proposed by eastern Co-operative Oncology Group were included in the study. After a detailed history and physical examination biopsy specimens were taken. All patients were given three cycles of neo-adjuvant chemotherapy consisting of cisplatin and 5-FU as continuous iv infusion at the intervals of 21 days. Patients then underwent surgery. All the samples including biopsy and surgery specimens were sent for immunohistochemistry.
Research Methodology: The study was a prospective analysis. The Chi Square test (χ2) with Yates correction factor and Fischer exact test (P value) were used.
Results: Of the total, 70% of cancer patients were positive for p53 and 60% were positive for c-myc mutations. The overall response rate was 36.6%. Statistically significant correlation was found between p53 & c-myc mutations, lymph node metastasis and response to chemotherapy. Significant correlation was also found between tumour grade and c-myc mutations.
Conclusion: The presence of p53 and c-myc mutations effect the overall response to anti-cancer drugs and the analyses of these tumour markers from biopsy specimens, can help select those patients can be selected who are more likely to respond to chemotherapy. Analysis of oncogenes for responsiveness of oral cancer patients to chemotherapy is likely to improve overall cure rates and reduce morbidity due to anti-neoplastic agents.
Keywords
References
Arango D, Corner GA, Wadler S, Catalano PJ, and Augenlicht LH. (2001). “C-myc/p53 interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo”, Cancer Res, Vol.61, pp.4910-4915.
Baral R, Patnaik S, and Das BR. (1998). “Co-overexpression of p53 and c-myc proteins linked with advanced stages of betel- and tobacco-related oral squamous cell carcinomas from eastern India”, Eur J Oral Sc, Vol.106(5), pp.907-913.
Bergamaschi D, Gasco M, Hiller L, Sullivan A, Syed N, Trigiante G, Yulug I, Merlano M, Numico G, Comino A, Attard M, Reelfs O, Gusterson B, Bell AK, Heath V, Tavassoli M, Farrell PJ, Smith P, Lu X, and Crook T. (2003). “P-53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis”, Cancer Cell, Vol.3, pp.387-402.
Biliran H, Jr., Banerjee S, Thakur A, Sarkar FH, Bollig A, Ahmed F, Wu J, Sun Y, and Liao JD. (2007). “C-Myc induced chemosensitization is mediated by suppression of cyclin D1 expression and nuclear factor-κB activity in pancreatic cancer cells”, Clin Cancer Res, Vol.13, pp.9 2811-2821.
Boyle Jo, Hakim J, Koch W, van der Riet PHruban RH, Roa RA, Correo R, Eby YJ, Ruppert JM, and Sidransky D. (1993). “The incidence of p53 mutations increases with progression of head and neck cancer”, Cancer Res, Vol.53(19), pp.4477-4480.
Cabelguenne A, Blons H, de Waziers I, Carnot F, Houllier AM, Soussi T, Brasnu D, Beaune P, Laccourreye O, and Puig PL. (2000). “P-53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series”, J ClinOncol, Vol.18, pp.1465-1473.
Cohen EEW, Lingen MW, and Vokes EE. (2004). “The expanding role of systemic therapy in head and neck cancer”, J ClinOncol, Vol.22, pp.1743-1752.
Fraser M,Leung BM, Yan X, Dan HC, Cheng JQ, and Tsang BK. (2003). “p53 Is a Determinant of X-Linked Inhibitor of Apoptosis Protein/Akt-Mediated Chemoresistance in Human Ovarian Cancer Cells”, Cancer Res, Vol.63, pp.21 7081-7088.
GedlickaC, Formanek M, Selzer E, Burian M, Kornfehl J, Fiebiger W, Cartellieri M, Marks B, and Kornek GV. (2002). “Phase II study with docetaxel and cisplatin in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck”, Oncology,Vol.63(2), pp.145-150.
KhuriFR, and Jain SR. (2004). “Novel agents and incremental advances in the treatment of head and neck cancer”, SeminOncol, Vol.31, pp.3-10.
Lamont EB, and Vokes EE. (2001). “Chemotherapy in the management of squamous-cell carcinoma of the head and neck”, Lancet Oncol, Vol.2, pp.261-269.
LicitraL, and Vermorken JB. (2004). “Is there still a role for neoadjuvant chemotherapy in head and neck cancer?”, Ann Oncol, Vol.15(1), pp.7-11.
Licitra L, Grandi C, Guzzo M, Mariani L, Vullo SL, Valvo F, Quattrone P, Valagussa P, Bonadonna G, Molinari R, and Cantu G. (2003). “Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial”, J ClinOncol, Vol.21, pp.327-333.
Miller AB, Hoogstraten B, Staquet M, and Winkler A. (1981). “Reporting results of cancer treatment”, Cancer, Vol.47, pp.207-214.
Mishra RC, Singh DN, and Mishra TK. (1996). “Post-operative radiotherapy in carcinoma of buccal mucosa, a prospective randomized trial”, Eur J SurgOncol, Vol.22, pp.502-504.
Misra S, Chaturvedi A, and Misra NC.(2008). “Management of Gingivobuccal Complex Cancer”, Ann R CollSurgEngl,Vol.90(7), pp.546-553.
Misra S, Chaturvedi A, and Misra NC. (2002). “Oral carcinoma”, In: Johnson Cd, and Taylor I. (eds). (2002). “Recent Advances in Surgery”, Royal Society of Medicine Press, London, Vol.25, pp.71-86.
Pan Q, Gorin MA, and Teknos TN. (2009). “Pharmacotherapy of head and neck squamous cell carcinoma”, Expert OpinPharmacother,Vol.10(14), pp.2291-2302.
Pich A, Margaria E, and Chiusa L. (2000). :Oncogenes and male breast carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival”, JCO, Vol.18(16), pp.2948-2956.
Pignon JP, Bourhis J, Domenge C, and Designe L. (2000). “Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data”, Lancet, Vol.355, pp.949-955.
Popović B, Jekić B, Novaković I, Luković L, Konstantinović V, Babić M, and Milasin J. (2010). “Cancer genes alterations and HPV infection in oral squamous cell carcinoma”, Int J Oral MaxillofacSurg, Vol.39(9), pp.909-915.
Porceddu SV, Campbell B, Rischin D, Corry J, Weih L, Guerrieri M, Grossi M, and Perers LJ. (2004).“Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma”, Int J RadiatOncolBiolPhys,Vol.60, pp.365-373.
Posner MR, Haddad RI, Wirth L, Norris CM, Goguen LA, Mahadevan A, Sullivan C, and Tishler RB.(2004). “Induction chemotherapy in locally advanced squamous cell cancer of the head and neck: evolution of the sequential treatment approach”, SeminOncol, Vol.31, pp.778-785.
Riva C, Lavieille JP, Reyt E, Brambilla E, Lunardi J, and Brambilla C. (1995). “Differential c-myc,c-jun& p53 expression in squamous cell carcinoma of head and neck: implications in drug resistence”, Eur J Cancer B Oral Oncol, Vol.31B(6), pp.384-391.
SobinLH, and Wittekind CH. (2002). “TNM Classification of Malignant Tumours”, 6th edition, Wiley-Liss, New York, Head and neck tumours: lip and oral cavity; pp.22-26.
Spaulding MB, Cartillo M, Lore J, Heffner H.(1992). “Surgery vs chemotherapy plus surgery for carcinoma head and neck”, Arch Otolaryngol Head & Neck Surg,Vol.118(3), pp.248-251.
Swaminathan U, Joshua E, Rao UK, and Ranganathan K. (2012). “Expression of p53 and Cyclin D1 in oral squamous cell carcinoma and normal mucosa: An immunohistochemical study”, J Oral Maxillofac Pathol, Vol.16, pp.172-177.
Wilson AJ, Velcich A, Arango D, Kurland AR, Shenoy SM, Pezo RC, Levsky JM, Singer RH, Augenlicht LH. (2002). “Novel Detection and Differential Utilization of a c-myc Transcriptional Block in Colon Cancer Chemoprevention”, Cancer Res., Vol.62(21), pp.21 6006-6010.
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