Cytodifferentiation and clinical outcome after chemotherapy and radiation therapy for rhabdomyosarcoma (RMS)

Med Pediatr Oncol. 2002 Jun;38(6):398-404. doi: 10.1002/mpo.10060.

Abstract

Background: Second-look surgery after therapy for rhabdomyosarcoma (RMS) may yield prognostic information regarding tumor responsiveness to treatment. Favorable outcome is suggested by tumor cells which have undergone maturation (cytodifferentiation).

Procedure: Specimens from patients treated on Intergroup RMS Study-IV (IRSG-IV) were studied before and after treatment. All patients received chemotherapy and most received radiation therapy. Post-treatment specimens were graded according to the quantity of tumor showing cytodifferentiation (0 = absent, 1 = mild, 2 = moderate, 3 = extensive). Proliferative activity by MIB-1, topoisomerase II-alpha, and p53 protein expression were measured.

Results: 19/31 cases from IRSG-IV were adequate for analysis. Six out of nineteen patients failed therapy within 1.3 years of treatment. Grade 3 cytodifferentiation was present in 10 cases (2 BRMS, 8 ERMS); none failed therapy. Grade 2 cytodifferentiation was present in 5 cases (1 ERMS, 2BRMS, 2ARMS); 2 patients with ARMS failed therapy. Grade 0-1 cytodifferentiation was present in 4 cases (1 ERMS and 3 ARMS); all failed therapy. Proliferative activity by MIB-1 and topoisomerase II-alpha immunohistochemistry decreased or was unchanged after treatment for all ERMS/BRMS, and 4/5 cases of ARMS. p53 immunohistochemistry showed no consistent pattern of reactivity. Sparse persistent tumor cells were present in 9/10 ERMS, 3/4 BRMS, 5/5 ARMS.

Conclusions: Extensive cytodifferentiation is more commonly seen in ERMS/BRMS compared with less evidence for cytodifferentiation in ARMS suggesting fundamentally different mechanisms of cellular response to therapy in RMS. Sparse persistent tumor cells in post treatment ERMS/BRMS specimens does not appear to affect outcome.

MeSH terms

  • Adolescent
  • Antigens, Neoplasm / analysis
  • Antigens, Nuclear
  • Biomarkers, Tumor / analysis
  • Cell Division
  • Cell Transformation, Neoplastic*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • DNA Topoisomerases, Type II / analysis
  • DNA-Binding Proteins
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Ki-67 Antigen
  • Male
  • Nuclear Proteins / analysis
  • Prognosis
  • Rhabdomyosarcoma / chemistry
  • Rhabdomyosarcoma / pathology*
  • Rhabdomyosarcoma / therapy*
  • Rhabdomyosarcoma, Alveolar / chemistry
  • Rhabdomyosarcoma, Alveolar / pathology
  • Rhabdomyosarcoma, Alveolar / therapy
  • Rhabdomyosarcoma, Embryonal / chemistry
  • Rhabdomyosarcoma, Embryonal / pathology
  • Rhabdomyosarcoma, Embryonal / therapy
  • Treatment Failure
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Antigens, Neoplasm
  • Antigens, Nuclear
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • DNA Topoisomerases, Type II