Mass biological profiling of cns tumours: Is it possible in india?

Ray, A.; Buffet, E.; Rutka, J. T.; Hawkins, C.
July 2007
Journal of Pediatric Neurosciences;Jul-Dec2007, Vol. 2 Issue 2, p102
Academic Journal
INTRODUCTION: Biological profiling of tumours to predict outcome is gaining increasing popularity in the western world. The paucity of equipment and the prohibitive costs have meant that such profiling has not been universally popular especially in the developing world. This paper tries to introduce the concept of 'biological profiling' using available equipment at minimal extra cost using medulloblastoma as an illustrative case. EXPERIMENTAL DESIGN: Clinical presentation and survival information were obtained for patients who had undergone surgery for MB at the Hospital for Sick Children between 1985 and 2001. A tissue microarray was constructed from their tumour samples. The arrays were assayed for immunohistochemical expression of MYC, p53, PDGFRα, ErbB2, MIB-1 and TrkC and for apoptosis (TUNEL). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival a weighted predictive score was calculated based on their hazard ratios (HR). The sum of these scores was then used to give an overall prediction of survival using a nomogram. RESULTS: The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR 2.02, P=0.01), and p53 (HR 2.29, P=0.02), TrkC (HR 0.65, P=0.14) and ErbB2 (HR 1.51, P=0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these hazard ratios. The 5-year survival rate for patients at the 10th, 50th and 90th percentiles of the score distribution were respectively 80.0%, 71.0%, and 35.7% with radiation therapy, and 70.5%, 58.5%, and 20.0% without radiation therapy. CONCLUSIONS: In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately, and establishes a framework for comparing prognostic markers in future clinical studies.


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