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


METHODS
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.
Smith
Lynn M
LM
Department of Radiation Oncology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA. lynn.m.smith@hsc.utah.edu
Anderson
James R
JR
Coffin
Cheryl M
CM
D000293:Adolescent; D000951:Antigens, Neoplasm / Q000032:analysis; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000473:pathology* / Q000628:therapy*; D018232:Rhabdomyosarcoma, Alveolar / Q000737:chemistry / Q000473:pathology / Q000628:therapy; D018233:Rhabdomyosarcoma, Embryonal / Q000737:chemistry / Q000473:pathology / Q000628:therapy; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II