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Prognostically Important Chromosomal Aberrations in Soft Tissue Sarcomas

A Report of the Chromosomes and Morphology (CHAMP) Study Group¹

Departments of Clinical Genetics [F. Me., N. M., F. Mi.), Occupational and Environmental Medicine [U. S.]), and Orthopedics [A. R.], Lund University Hospital, SE-221 85 Lund, Sweden; Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts 02115 [P. D. C., C. D. M. F.]; Departments of Oncologic Surgery [I. D. W.] and Pathology [R. S.], and the Center for Human Genetics and Flanders Institute of Biotechnology [H. V. D. B.], University of Leuven, B3000 Leuven, Belgium; Department of Pathology, Istituto Nazionale Tumori, 20133 Milan, Italy [J. R.]; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510 [G. T.]; Dip Scienze Applicate ai Biosistemi, Cittadella Universitaria, 09042 Cagliari, Italy [R. V.]; and the Department of Pathology and Cytology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden [H. W.]

Cytogenetic analysis has not only provided important information on thepathogenesis of soft tissue tumors but, by disclosing distinct chromosomal rearrangements in different histopathological entities, has also come to serve as a valuable diagnostic tool. Little is known as yet about the potential prognostic impact of cytogenetic features detected in these tumors. A total of 239 benign and 221 malignant soft tissue tumors with clonal chromosome aberrations were subdivided according to general karyotypic features, such as degree of complexity and ploidy level, and rearrangements of specific chromosomal regions. The cytogenetic variables were analyzed regarding clinical outcome, using time to metastasis as the end point. Selected variables were then compared with established clinicopathological predictors of metastasis development. When the entire material was considered, 167 of 268 investigated cytogenetic variables were associated with clinical outcome. Focusing on the subset of 151 patients with high-grade sarcoma, 17 variables were identified that, besides grade and size, were associated with increased risk of metastasis development. A final Cox regression analysis identified five independent cytogenetic predictors of adverse outcome; breakpoints in chromosome regions 1p1, 1q4, 14q1, and 17q2, and gain of regions 6p1/p2. An increasing effect on metastatic risk was seen with increasing involvement of the selected cytogenetic variables, even when different histopathological types were studied separately. We conclude that cytogenetic data provide independent prognostic information in soft tissue sarcomas. Furthermore, our results point to specific areas of the genome harboring genes that may influence the metastatic potential of sarcoma cells.

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				F. Mertens, U. Stromberg, A. Rydholm, P. Gustafson, H. C.F. Bauer, O. Brosjo, and N. Mandahl Prognostic Significance of Chromosome Aberrations in High-Grade Soft Tissue Sarcomas J. Clin. Oncol., January 10, 2006; 24(2): 315 - 320. [Abstract] [Full Text] [PDF]