Results of a prospective minimal disseminated disease study in human rhabdomyosarcoma using three different molecular markers

Francesca Sartori, Rita Alaggio, Giulio Zanazzo, Alberto Garaventa, Andrea Di Cataldo, Modesto Carli, Angelo Rosolen

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Rhabdomyosarcoma (RMS) has 2 major histologie subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is more aggressive and prone to distant tumor dissemination, whereas ERMS tends to expand and recur locally. Little information is available on bone marrow involvement by RMS. METHODS. We determined the sensitivity and specificity of MyoD1, myogenin, and PAX-FKHR transcripts as RMS markers and used them to study prospectively by reverse-transcriptase polymerase chain reaction (RT-PCR) a series of consecutive unselected RMS patients enrolled in the Italian Association of Pediatric Hematology and Oncology national trial. Prevalence of minimal disseminated disease (MDD) and its response kinetics to chemotherapy were assessed. RESULTS. MyoD1 and myogenin were specifically associated with RMS, independently of histologic subtype, whereas PAX3/7-FKHR transcripts were expressed only in ARMS. Sensitivity was higher for MyoD1 compared with myogenin and PAX-FKHR. Out of a cohort of 40 patients, MDD positively was limited to ARMS, with the sole exception of 1 ERMS. Prevalence of MDD positivity increased when a real-time polymerase chain reaction approach was used on a subgroup of patients. RT-PCR was more sensitive than microscopic examination of bone marrow biopsies. The study of the response kinetics of MDD showed that in approximately half of the cases, bone marrow was cleared of disease after 1 cycle of chemotherapy. CONCLUSIONS. MyoD1 and myogenin transcripts can be used as tumor markers for MDD assessment in virtually all UMS cases, whereas PAX-FKHR is specific for ARMS. Sensitivity of RT-PCR methods was superior compared with standard morphologic assays. Our study suggests that bone marrow involvement is more common in ARMS compared with ERMS, and that MDD can be often cleared by the initial chemotherapy cycles.

Original languageEnglish
Pages (from-to)1766-1775
Number of pages10
JournalCancer
Volume106
Issue number8
DOIs
Publication statusPublished - May 15 2006

Keywords

  • Bone marrow
  • MRD
  • MyoD1
  • Rhabdomyosarcoma
  • RT-PCR

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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