Abstract
Purpose: Clinico-epidemiological studies show that the behaviour of the tongue cancer is different from the cancer originating at other sites of the oral cavity. However, studies identifying the reason for such difference are lacking in the literature. Methods: In the present study, we have attempted to see whether any difference existed in the cell cycle regulatory mechanism of these tumours by comparing immunohistochemically the expression of major cell cycle regulatory proteins in 147 buccal and 94 tongue carcinoma (anterior two-third of tongue) prospectively. Results: On comparison of buccal and tongue carcinoma, expression of p16 and p21 showed significant difference. In combined analysis, simultaneous down regulation of p16 and p21 was seen in 47% of tongue cancer cases as against 28% in buccal carcinoma (P=0.004). In univariate analysis, none of the clinico-biological variables studied showed significant association with survival in tongue carcinoma, whereas, some of the clinico-biological variables associated with survival in buccal carcinoma. Among the biological markers, the overexpression of cyclin D1 (P=0.007) and p53, detected using both the clones of antibodies—DO7 (P=0.008) and PAb240 (P=0.014) and the down regulation of p16 (0.033), showed significant association with shorter disease free survival (DFS) in these cases. Whereas in the case of overall survival (OS), overexpression of p53 [DO7 (P=0.031) and PAb240 (P=0.017)] and cyclin D1 (P=0.001) associated with poor survival. In multivariate analysis, the expression pattern of p53 and p16 protein influences the DFS whereas cyclin D1 expression showed independent association with the OS in buccal carcinoma. Conclusions: Thus, tongue and buccal cancers represent different biological subentities, and such differences should be considered in oral cancer management.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Babu KG (2001) Oral cancers in India. Semin Oncol 28:169–173
Bova RJ, Quinn DI, Nankervis JS, Cole IE, Sheridan BF, Jensen MJ, Morgan GJ, Hughes CJ, Sutherland RL (1999) Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue. Clin Cancer Res 5:2810–2819
Casiglia J, Woo SB (2001) A comprehensive review of oral cancer. Gen Dent 49:72–82
Coqueret O (2002) Linking cyclins to transcriptional control. Gene 299:35–55
Delavaine L, La Thangue NB (1999) Control of E2F activity by p21Waf1/Cip1. Oncogene 18:5381–5392
Dotto GP (2000) p21(WAF1/Cip1): more than a break to the cell cycle? Biochim Biophys Acta 1471:M43–M56
Freier K, Bosch FX, Flechtenmacher C, Devens F, Benner A, Lichter P, Joos S, Hofele C (2003a) Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis. Anticancer Res 23:3971–3977
Freier K, Joos S, Flechtenmacher C, Devens F, Benner A, Bosch FX, Lichter P, Hofele C (2003b) Tissue microarray analysis reveals site-specific prevalence of oncogene amplifications in head and neck squamous cell carcinoma. Cancer Res 63:1179–1182
Goto H, Kawano K, Kobayashi I, Sakai H, Yanagisawa S (2002) Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue. Oral Oncol 38:549–556
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Howaldt HP, Kainz M, Euler B, Vorast H (1999) Proposal for modification of the TNM staging classification for cancer of the oral cavity. DOSAK. J Craniomaxillofac Surg 27:275–288
Jayasurya R, Francis G, Kannan S, Lekshminarayanan K, Nalinakumari KR, Abraham T, Abraham EK, Nair MK (2004) p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma. Int J Cancer 109:710–716
Jayasurya R, Sathyan KM, Lakshminarayanan K, Abraham T, Nalinakumari KR, Abraham EK, Nair MK, Kannan S (2005) Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma. Mod Pathol 18:1056–1066
Kannan S, Tahara H, Yokozaki H, Mathew B, Nalinakumari KR, Nair MK, Tahara E (1997) Telomerase activity in premalignant and malignant lesions of human oral mucosa. Cancer Epidemiol Biomarkers Prev 6:413–420
Kwong RA, Nguyen TV, Bova RJ, Kench JG, Cole IE, Musgrove EA, Henshall SM, Sutherland RL (2003) Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res 9:3705–3711
Landis SH, Murray T, Bolden S, Wingo PA (1998) Cancer statistics, 1998. CA Cancer J Clin 48:6–29
Lim SC, Zhang S, Ishii G, Endoh Y, Kodama K, Miyamoto S, Hayashi R, Ebihara S, Cho JS, Ochiai A (2004) Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue. Clin Cancer Res 10:166–172
Liu CJ, Chang KW, Chao SY, Kwan PC, Chang SM, Yen RY, Wang CY, Wong YK (2004) The molecular markers for prognostic evaluation of areca-associated buccal squamous cell carcinoma. J Oral Pathol Med 33:327–334
Mineta H, Miura K, Takebayashi S, Ueda Y, Misawa K, Harada H, Wennerberg J, Dictor M (2000) Cyclin D1 overexpression correlates with poor prognosis in patients with tongue squamous cell carcinoma. Oral Oncol 36:194–198
Moore SR, Johnson NW, Pierce AM, Wilson DF (2000) The epidemiology of tongue cancer: a review of global incidence. Oral Dis 6:75–84
Niwa S, Ueno S, Shirasu R (2001) Alteration of pRb expression in the development of rat tongue carcinoma induced by 4-nitroquinoline 1-oxide. Oral Oncol 37:579–585
Ogi K, Toyota M, Ohe-Toyota M, Tanaka N, Noguchi M, Sonoda T, Kohama G, Tokino T (2002) Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma. Clin Cancer Res 8:3164–3171
Parkin DM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49:33–64, 1
Paterson IC, Eveson JW, Prime SS (1996) Molecular changes in oral cancer may reflect aetiology and ethnic origin. Eur J Cancer B Oral Oncol 32B:150–153
Pindborg JJ, Reichart PA, Smith CJ, van der Waal I (1997) WHO-histological typing of cancer and precancer of the oral mucosa. 2nd edn. Springer, Berlin Heidelberg New York
Ruas M, Peters G (1998) The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1378:F115–F177
Schwartz JL, Gu X, Kittles RA, Baptiste A, Shklar G (2000) Experimental oral carcinoma of the tongue and buccal mucosa: possible biologic markers linked to cancers at two anatomic sites. Oral Oncol 36:225–235
Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677
Vora HH, Shah NG, Patel DD, Trivedi TI, Chikhlikar PR (2003) Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis. J Surg Oncol 82:34–50
Acknowledgement
This work was supported by Indian Council of Medical Research through their Grant, No. 5/13/24/96-NCD-III.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sathyan, K.M., Sailasree, R., Jayasurya, R. et al. Carcinoma of tongue and the buccal mucosa represent different biological subentities of the oral carcinoma. J Cancer Res Clin Oncol 132, 601–609 (2006). https://doi.org/10.1007/s00432-006-0111-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-006-0111-y