Prognostication of Soft Tissue Sarcomas Based on Chromosome 17q Gene and Protein Status: Evaluation of TOP2A, HER-2/neu, and Survivin

• Published in: Annals of surgical oncology 2012-06, Vol.19 (6), p.1790-1799
• Main Authors: da Cunha, Isabela Werneck, De Brot, Louise, Carvalho, Kátia Cândido, Rocha, Rafael Malagoli, Fregnani, José Humberto, Falzoni, Roberto, de Oliveira Ferreira, Fábio, Júnior, Samuel Aguiar, Lopes, Ademar, Muto, Nair Hideko, Reis, Luiz F. L., Soares, Fernando Augusto, Vassallo, José
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bone and Soft Tissue Sarcomas; Chromosomes, Human, Pair 17 - genetics; DNA Topoisomerases, Type II - genetics; DNA Topoisomerases, Type II - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fibroma - mortality; Fibroma - pathology; Fibroma - therapy; Fibromatosis, Aggressive - mortality; Fibromatosis, Aggressive - pathology; Fibromatosis, Aggressive - therapy; Follow-Up Studies; Gene Amplification; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oncology; Poly-ADP-Ribose Binding Proteins; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Sarcoma - mortality; Sarcoma - pathology; Sarcoma - therapy; Sarcoma, Synovial - mortality; Sarcoma, Synovial - pathology; Sarcoma, Synovial - therapy; Surgery; Surgical Oncology; Survival Rate; Young Adult
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-2184-3

Background Topoisomerase 2 alpha ( TOP2A ), HER-2/ neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value. Methods Eighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray. Results TOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes. Conclusions These findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.