Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma

David N. Shapiro, David M. Parham, Edwin C. Douglass, Richard Ashmun, Bruce L. Webber, William A. Newton, Michael L. Hancock, Harold M. Maurer, A. Thomas Look

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P < .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P < .001 ; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalJournal of Clinical Oncology
Volume9
Issue number1
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shapiro, D. N., Parham, D. M., Douglass, E. C., Ashmun, R., Webber, B. L., Newton, W. A., Hancock, M. L., Maurer, H. M., & Thomas Look, A. (1991). Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma. Journal of Clinical Oncology, 9(1), 159-166. https://doi.org/10.1200/JCO.1991.9.1.159