Original contribution MAPK7 and MAP2K4 as prognostic markers in osteosarcoma ☆ Francine Tesser-Gamba MSc a,b , Antonio Sergio Petrilli MD, PhD a , Maria Teresa de Seixas Alves MD, PhD a,c , Reynaldo Jesus Garcia Filho MD, PhD d , Yara Juliano PhD e , Sílvia Regina Caminada Toledo PhD a,b, ⁎ a Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil b Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil c Department of Pathology, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil d Department of Orthopedic Surgery and Traumatology, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil e Department of Public Health, University of Santo Amaro, São Paulo, SP 04829-300, Brazil Received 15 April 2011; revised 10 August 2011; accepted 12 August 2011 Keywords: Osteosarcoma (OS); Gene expression; OS markers; MAPK7; MAP2K4 Summary Osteosarcoma is a class of cancer originating from the bone, affecting mainly children and young adults. Cytogenetic studies showed the presence of rearrangements and recurrent gains in specific chromosomal regions, indicating the possible involvement of genes located in these regions during the pathogenesis of osteosarcoma. These studies investigated expression of 10 genes located in the chromosomal region involved in abnormalities in osteosarcoma, 1p36, 17p, and chromosome 19. The purpose of this study was to investigate the expression profile of genes located in regions involved in chromosomal rearrangements in osteosarcoma. We used quantitative real-time polymerase chain reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR, ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30 postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control sample. The most interesting results showed a strong association between the expression levels of MAPK7 and MAP2K4 genes and clinical parameters of osteosarcoma. Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis. Thus, these genes could be good markers in assessing response to treatment and development of osteosarcoma. © 2012 Elsevier Inc. All rights reserved. ☆ This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (São Paulo, Brazil), Grant nos. 07/53869-3 and 07/02693-2, and Grupo de Apoio ao Adolescente e à Criança com Câncer/Federal University of São Paulo (São Paulo, Brazil). ⁎ Corresponding author. Pediatrics Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, Rua Botucatu, São Paulo, SP 04023-062, Brazil. E-mail addresses: francine.tesser@yahoo.com.br (F. Tesser-Gamba), sergiopetrilli@graacc.org.br (A. S. Petrilli), mtseixas@patologia.epm.br (M. T. de Seixas Alves), jesusgarcia.dot@epm.br (R. J. G. Filho), yjuliano@unisa.br (Y. Juliano), silviatoledo@graacc.org.br (S. R. C. Toledo). www.elsevier.com/locate/humpath 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2011.08.003 Human Pathology (2012) 43, 994–1002