R Jayasurya

Regional Cancer Centre, Thiruvananthapuram, Kerala, India

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Publications (3)12.79 Total impact

  • Article: Carcinoma of tongue and the buccal mucosa represent different biological subentities of the oral carcinoma.
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    ABSTRACT: 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. 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. 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. Thus, tongue and buccal cancers represent different biological subentities, and such differences should be considered in oral cancer management.
    Journal of Cancer Research and Clinical Oncology 10/2006; 132(9):601-9. · 2.56 Impact Factor
  • Article: Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma.
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    ABSTRACT: The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P=0.016), cyclin D1 (P=0.0001) and p16 (P=0.012) showed significant association with disease-free survival, and p16 (P=0.041) and cyclin D1 (P=<0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies.
    Modern Pathology 09/2005; 18(8):1056-66. · 4.79 Impact Factor
  • Article: p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma.
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    ABSTRACT: Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.
    International Journal of Cancer 06/2004; 109(5):710-6. · 5.44 Impact Factor