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 Schleiermacher, G. Articles by Delattre, O. Search for Related Content PubMed PubMed Citation Articles by Schleiermacher, G. Articles by Delattre, O. Social Bookmarking                            What's this?

Increased Risk of Systemic Relapses Associated With Bone Marrow Micrometastasis and Circulating Tumor Cells in Localized Ewing Tumor

Gudrun Schleiermacher, Martine Peter, Odile Oberlin, Thierry Philip, Hervé Rubie, Françoise Mechinaud, Danièle Sommelet-Olive, Judith Landman-Parker, Danièle Bours, Jean Michon, Olivier Delattre for the Société Française d’Oncologie Pédiatrique

From the Laboratoire de Pathologie Moléculaire des Cancers, INSERM U 509, Section de Recherche, and Laboratoire de Transfert, and Unité de Biostatistique, and Département d’Oncologie Pédiatrique, Institut Curie, and Service d’Hémato-Oncologie Pédiatrique, Hôpital Trousseau, Paris; Département d’Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif; Service de Pédiatrie, Centre Léon Bérard, Lyon; Service d’Hématologie Oncologie, Hôpital des Enfants, Toulouse; Service d’Oncologie Pédiatrique, CHU de Nantes, Nantes; and Service de Médecine Infantile, Hôpital des Enfants, Vanduvre, France.

Address reprint requests to Olivier Delattre, MD, PhD, Laboratoire de Pathologie Moléculaire des Cancers, L’Institut National de la Santé et de la Recherche Médicale, U 509, 26 rue d’Ulm, 75248 Paris Cedex 05, France; email: delattre{at}curie.fr.

Purpose: The presence of metastasis is a major prognostic factor in Ewing tumor (ET). The relapse pattern of patients with localized tumors has long indicated that cases with disseminated ET cells escape detection at diagnosis. ET cells are characterized by specific gene fusions that can be detected with high sensitivity and specificity by reverse transcriptase polymerase chain reaction (RT-PCR).

Patients and Methods: RT-PCR targeting EWS-FLI-1 or EWS-ERG transcripts was used to search for occult tumor cells in peripheral blood (PB) and bone marrow (BM) at diagnosis in 172 patients with ET, and the prognostic significance of this parameter was assessed.

Results: As we suggested previously in a smaller series of patients, RT-PCR positivity of the BM was correlated with a high risk of adverse outcome in the overall study population (P = .007). More interestingly, among patients with otherwise localized tumors, BM micrometastasis also predicted significantly poorer disease-free survival rates (P = .043). The presence of circulating tumor cells (CTC) was more frequently observed in patients with large tumors (P = .006). CTC were associated with a poor outcome among patients with clinically localized disease (P = .045). Patients with clinically localized disease and peripheral occult tumor cells as evidenced by BM and/or PB RT-PCR positivity had axial or proximal tumors and experienced relapses at a systemic rather than at a local level.

Conclusion: Patients with localized ET and BM micrometastasis or CTC are comparable to patients with metastases in terms of the localization of the primary tumor, outcome, and relapse pattern.

Supported in part by grants from the Programme Hospitalier de Recherche Clinique, the Plateforme de Soutien au Transfert et à la Recherche Clinique, the Association pour la Recherche contre le Cancer, the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, the Institut Curie, and the Institut National de la Santé et de la Recherche Médicale, Paris, France.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. Diomedi-Camassei, H. P. McDowell, M. A. De Ioris, S. Uccini, P. Altavista, G. Raschella, R. Vitali, O. Mannarino, L. De Sio, D. A. Cozzi, et al. Clinical Significance of CXC Chemokine Receptor-4 and c-Met in Childhood Rhabdomyosarcoma Clin. Cancer Res., July 1, 2008; 14(13): 4119 - 4127. [Abstract] [Full Text] [PDF]

				C. Rodriguez-Galindo, F. Navid, T. Liu, C. A. Billups, B. N. Rao, and M. J. Krasin Prognostic factors for local and distant control in Ewing sarcoma family of tumors Ann. Onc., April 1, 2008; 19(4): 814 - 820. [Abstract] [Full Text] [PDF]

				I. Y. Cheung, Y. Feng, K. Danis, N. Shukla, P. Meyers, M. Ladanyi, and N.-K. V. Cheung Novel Markers of Subclinical Disease for Ewing Family Tumors from Gene Expression Profiling Clin. Cancer Res., December 1, 2007; 13(23): 6978 - 6983. [Abstract] [Full Text] [PDF]

				M.-P. Castex, H. Rubie, M. C.G. Stevens, C. C. Escribano, J. S. de Gauzy, A. Gomez-Brouchet, A. Rey, O. Delattre, and O. Oberlin Extraosseous Localized Ewing Tumors: Improved Outcome With Anthracyclines--The French Society of Pediatric Oncology and International Society of Pediatric Oncology J. Clin. Oncol., April 1, 2007; 25(10): 1176 - 1182. [Abstract] [Full Text] [PDF]

				M. Bernstein, H. Kovar, M. Paulussen, R. L. Randall, A. Schuck, L. A. Teot, and H. Juergensg Ewing's Sarcoma Family of Tumors: Current Management. Oncologist, May 1, 2006; 11(5): 503 - 519. [Abstract] [Full Text] [PDF]

				O. S. Bruland, H. Hoifodt, G. Saeter, S. Smeland, and O. Fodstad Hematogenous Micrometastases in Osteosarcoma Patients Clin. Cancer Res., July 1, 2005; 11(13): 4666 - 4673. [Abstract] [Full Text] [PDF]

				J.-Y. Pierga, C. Bonneton, A. Vincent-Salomon, P. de Cremoux, C. Nos, N. Blin, P. Pouillart, J.-P. Thiery, and H. Magdelenat Clinical Significance of Immunocytochemical Detection of Tumor Cells Using Digital Microscopy in Peripheral Blood and Bone Marrow of Breast Cancer Patients Clin. Cancer Res., February 15, 2004; 10(4): 1392 - 1400. [Abstract] [Full Text] [PDF]

				A. Ohali, S. Avigad, I.J. Cohen, I. Meller, Y. Kollender, J. Issakov, I. Gelernter, Y. Goshen, I. Yaniv, and R. Zaizov Association Between Telomerase Activity and Outcome in Patients With Nonmetastatic Ewing Family of Tumors J. Clin. Oncol., October 15, 2003; 21(20): 3836 - 3843. [Abstract] [Full Text] [PDF]