This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grotzer, M. A. Articles by Trojanowski, J. Q. Search for Related Content PubMed PubMed Citation Articles by Grotzer, M. A. Articles by Trojanowski, J. Q.

TrkC Expression Predicts Good Clinical Outcome in Primitive Neuroectodermal Brain Tumors

From the Division of Oncology, Human Genetics, Biostatistics, and Neurosurgery and Department of Pathology, The Children’s Hospital of Philadelphia; and Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.

Address reprint requests to J.Q. Trojanowski, MD, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104; email trojanow{at}mail.med upenn.edu.

PURPOSE: To identify biologic prognostic factors in childhood primitive neuroectodermal tumors (PNET), including medulloblastoma, that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity.

PATIENTS AND METHODS: We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterized PNET patients using in situ hybridization. Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis.

RESULTS: High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most powerful predictor of outcome (hazards ratio, 4.81; P < .00005), exceeding all clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P < .00005).

CONCLUSION: High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome. Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials.

This article has been cited by other articles:

				R. J. Packer and G. Vezina Management of and Prognosis With Medulloblastoma: Therapy at a Crossroads Arch Neurol, November 1, 2008; 65(11): 1419 - 1424. [Abstract] [Full Text] [PDF]

				R. J. Packer Childhood Brain Tumors: Accomplishments and Ongoing Challenges J Child Neurol, October 1, 2008; 23(10): 1122 - 1127. [Abstract] [PDF]

				I. F. Pollack Diagnostic and Therapeutic Stratification of Childhood Brain Tumors: Implications for Translational Research J Child Neurol, October 1, 2008; 23(10): 1179 - 1185. [Abstract] [PDF]

				T. J. MacDonald Aggressive Infantile Embryonal Tumors J Child Neurol, October 1, 2008; 23(10): 1195 - 1204. [Abstract] [PDF]

				W. Jin, C. Yun, J. Jeong, Y. Park, H.-D. Lee, and S.-J. Kim c-Src Is Required for Tropomyosin Receptor Kinase C (TrkC)-induced Activation of the Phosphatidylinositol 3-Kinase (PI3K)-AKT Pathway J. Biol. Chem., January 18, 2008; 283(3): 1391 - 1400. [Abstract] [Full Text] [PDF]

				W. Jin, C. Yun, H.-S. Kim, and S.-J. Kim TrkC Binds to the Bone Morphogenetic Protein Type II Receptor to Suppress Bone Morphogenetic Protein Signaling Cancer Res., October 15, 2007; 67(20): 9869 - 9877. [Abstract] [Full Text] [PDF]

				S. Rutkowski, A. von Bueren, K. von Hoff, W. Hartmann, T. Shalaby, F. Deinlein, M. Warmuth-Metz, N. Soerensen, A. Emser, U. Bode, et al. Prognostic Relevance of Clinical and Biological Risk Factors in Childhood Medulloblastoma: Results of Patients Treated in the Prospective Multicenter Trial HIT'91 Clin. Cancer Res., May 1, 2007; 13(9): 2651 - 2657. [Abstract] [Full Text] [PDF]

				S. H. Ramkissoon, P. S. Patel, M. Taborga, and P. Rameshwar Nuclear Factor-{kappa}B Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma Cancer Res., February 15, 2007; 67(4): 1653 - 1659. [Abstract] [Full Text] [PDF]

				R. J. Packer, A. Gajjar, G. Vezina, L. Rorke-Adams, P. C. Burger, P. L. Robertson, L. Bayer, D. LaFond, B. R. Donahue, M. H. Marymont, et al. Phase III Study of Craniospinal Radiation Therapy Followed by Adjuvant Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma J. Clin. Oncol., September 1, 2006; 24(25): 4202 - 4208. [Abstract] [Full Text] [PDF]

				H. J. Patel, S. H. Ramkissoon, P. S. Patel, and P. Rameshwar Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides PNAS, November 29, 2005; 102(48): 17436 - 17441. [Abstract] [Full Text] [PDF]

				D. W. Ellison, O. E. Onilude, J. C. Lindsey, M. E. Lusher, C. L. Weston, R. E. Taylor, A. D. Pearson, and S. C. Clifford {beta}-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee J. Clin. Oncol., November 1, 2005; 23(31): 7951 - 7957. [Abstract] [Full Text] [PDF]

				J. R. Geyer, R. Sposto, M. Jennings, J. M. Boyett, R. A. Axtell, D. Breiger, E. Broxson, B. Donahue, J. L. Finlay, J. W. Goldwein, et al. Multiagent Chemotherapy and Deferred Radiotherapy in Infants With Malignant Brain Tumors: A Report From the Children's Cancer Group J. Clin. Oncol., October 20, 2005; 23(30): 7621 - 7631. [Abstract] [Full Text] [PDF]

				P. Brouwers Commentary: Study of the Neurobehavioral Consequences of Childhood Cancer: Entering the Genomic Era? J. Pediatr. Psychol., January 1, 2005; 30(1): 79 - 84. [Full Text] [PDF]

				A. Ray, M. Ho, J. Ma, R. K. Parkes, T. G. Mainprize, S. Ueda, J. McLaughlin, E. Bouffet, J. T. Rutka, and C. E. Hawkins A Clinicobiological Model Predicting Survival in Medulloblastoma Clin. Cancer Res., November 15, 2004; 10(22): 7613 - 7620. [Abstract] [Full Text] [PDF]

				J. M. Lamont, C. S. McManamy, A. D. Pearson, S. C. Clifford, and D. W. Ellison Combined Histopathological and Molecular Cytogenetic Stratification of Medulloblastoma Patients Clin. Cancer Res., August 15, 2004; 10(16): 5482 - 5493. [Abstract] [Full Text] [PDF]

				O. Ozen, B. Krebs, B. Hemmerlein, A. Pekrun, H. Kretzschmar, and J. Herms Expression of Matrix Metalloproteinases and Their Inhibitors in Medulloblastomas and Their Prognostic Relevance Clin. Cancer Res., July 15, 2004; 10(14): 4746 - 4753. [Abstract] [Full Text] [PDF]

				A. Fernandez-Teijeiro, R. A. Betensky, L. M. Sturla, J. Y.H. Kim, P. Tamayo, and S. L. Pomeroy Combining Gene Expression Profiles and Clinical Parameters for Risk Stratification in Medulloblastomas J. Clin. Oncol., March 15, 2004; 22(6): 994 - 998. [Abstract] [Full Text] [PDF]

				A. Gajjar, R. Hernan, M. Kocak, C. Fuller, Y. Lee, P. J. McKinnon, D. Wallace, C. Lau, M. Chintagumpala, D. M. Ashley, et al. Clinical, Histopathologic, and Molecular Markers of Prognosis: Toward a New Disease Risk Stratification System for Medulloblastoma J. Clin. Oncol., March 15, 2004; 22(6): 984 - 993. [Abstract] [Full Text] [PDF]

				P. G. Fisher, P. C. Burger, and C. G. Eberhart Biologic Risk Stratification of Medulloblastoma: The Real Time Is Now J. Clin. Oncol., March 15, 2004; 22(6): 971 - 974. [Full Text] [PDF]

				C. Pingoud-Meier, D. Lang, A. J. Janss, L. B. Rorke, P. C. Phillips, T. Shalaby, and M. A. Grotzer Loss of Caspase-8 Protein Expression Correlates with Unfavorable Survival Outcome in Childhood Medulloblastoma Clin. Cancer Res., December 15, 2003; 9(17): 6401 - 6409. [Abstract] [Full Text] [PDF]

				W. Q. Yang, D. Senger, H. Muzik, Z. Q. Shi, D. Johnson, P. M. A. Brasher, N. B. Rewcastle, M. Hamilton, J. Rutka, J. Wolff, et al. Reovirus Prolongs Survival and Reduces the Frequency of Spinal and Leptomeningeal Metastases from Medulloblastoma Cancer Res., June 15, 2003; 63(12): 3162 - 3172. [Abstract] [Full Text] [PDF]

				T. J. MacDonald, B. R. Rood, M. R. Santi, G. Vezina, K. Bingaman, P. H. Cogen, and R. J. Packer Advances in the Diagnosis, Molecular Genetics, and Treatment of Pediatric Embryonal CNS Tumors Oncologist, April 1, 2003; 8(2): 174 - 186. [Abstract] [Full Text] [PDF]

				Luis Del Valle, S. Enam, A. Lassak, J. Y. Wang, S. Croul, K. Khalili, and K. Reiss Insulin-like Growth Factor I Receptor Activity in Human Medulloblastomas Clin. Cancer Res., June 1, 2002; 8(6): 1822 - 1830. [Abstract] [Full Text] [PDF]

				M. A. Grotzer, M. D. Hogarty, A. J. Janss, X. Liu, H. Zhao, A. Eggert, L. N. Sutton, L. B. Rorke, G. M. Brodeur, and P. C. Phillips MYC Messenger RNA Expression Predicts Survival Outcome in Childhood Primitive Neuroectodermal Tumor/Medulloblastoma Clin. Cancer Res., August 1, 2001; 7(8): 2425 - 2433. [Abstract] [Full Text] [PDF]

				A. Eggert, M. A. Grotzer, N. Ikegaki, H. Zhao, A. Cnaan, G. M. Brodeur, and A. E. Evans Expression of the Neurotrophin Receptor TrkB Is Associated With Unfavorable Outcome in Wilms' Tumor J. Clin. Oncol., February 1, 2001; 19(3): 689 - 696. [Abstract] [Full Text] [PDF]

				J. A. Biegel, B. Fogelgren, J.-Y. Zhou, C. D. James, A. J. Janss, J. C. Allen, D. Zagzag, C. Raffel, and L. B. Rorke Mutations of the INI1 Rhabdoid Tumor Suppressor Gene in Medulloblastomas and Primitive Neuroectodermal Tumors of the Central Nervous System Clin. Cancer Res., July 1, 2000; 6(7): 2759 - 2763. [Abstract] [Full Text]