The expression pattern of contractile and intermediate filament proteins in developing skeletal muscle and rhabdomyosarcoma of childhood: Diagnostic and prognostic utility

Abstract

In order to investigate whether rhabdomyosarcoma (RMS) can be related to equivalent stages of skeletal muscle development, muscle tissue of 21 human foetuses and 112 primary RMSs were characterized immunohistochemically using antibodies directed against vimentin, desmin, muscle-specific actin (HHF35), sarcomeric actin (sr-actin), smooth muscle actin (sm-actin), and troponin-T. During fetal skeletal muscle development, all myotubes/fibres of the first and second generations expressed desmin, HHF35, and sr-actin. Vimentin was almost exclusively present in immature primary and secondary myotubes/fibres. Troponin-T was expressed in immature myotubes/fibres of the first and second generations as well as mature fibres of the second generation. Sm-actin was never expressed. Vimentin was expressed in 96 per cent of primary and 98 per cent of relapsed RMS; HHF35 in 96 and 98 per cent, respectively; desmin in 95 and 100 per cent; troponin-T in 82 and 75 per cent; sr-actin in 71 and 86 per cent; and sm-actin in 13 and 17 per cent. The proportion of RMS cells reacting with vimentin, HHF35, and desmin was consistently higher than those expressing sr-actin and troponin-T. Neither the shape nor size of neoplastic RMS cells nor the histopathological types were related to the expression pattern of the investigated markers. RMS with aberrant expression of two or more markers predicted a worse prognosis than RMS in which at most one marker was aberrantly expressed (25 per cent and 54 per cent 10-year survival, P = 0.01). These results demonstrate that HHF35, desmin, sr-actin, and troponin-T have the potential to confirm the commitment of the tumours to the myogenic pathway which supports the diagnosis of RMS. However, it was impossible to relate RMS to equivalent stages of skeletal muscle development. Aberrant marker expression by RMS cells correlated significantly with patients' survival.

GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells

“…Treatment with lower doses of GR-891 modified the expression of desmin, vimentin and α-actinin, leading to a greater degree of organization of myofilaments in treated cells with a gradual substitution of vimentin by desmin and a uniform, linear distribution of α-actinin filaments along the actin myofilaments. These changes suggest that RD cells had re-entered the programme of muscle maturation and subsequently underwent a process similar to myogenesis (Burridge and Feramisco, 1981;Capetanaki et al, 1984;Wijnaendts et al, 1994). Minor changes in the degree of protein organization were observed with 5-FU, suggesting that its cytotoxic effect (Waxman et al, 1990(Waxman et al, , 1992Lesuffleur et al, 1991a,b) hindered complete differentiation.…”

“…Morphological changes in RD cells were accompanied by modifications in the expression of differentiation markers (Carter et al, 1989;Prados et al, 1993;Wijnaendts et al, 1994). Treatment with lower doses of GR-891 modified the expression of desmin, vimentin and α-actinin, leading to a greater degree of organization of myofilaments in treated cells with a gradual substitution of vimentin by desmin and a uniform, linear distribution of α-actinin filaments along the actin myofilaments.…”

Synthesis and evaluation of new 5-fluorouracil antitumor cell differentiating derivatives

“…The RD cells treated with the different doses of drugs modified the expression of desmin and vimentin proteins similar to the process of normal myogenesis 28 with a substitution of vimentin by desmin. Desmin protein is used as a differentiation marker in the developing, 29 whereas a largest vimentin expression is found in poorly differentiated and highly aggressive tumours.…”

MARP Protein Family: A Possible Role in Molecular Mechanisms of Tumorigenesis

“…Immunohistochemical analysis of muscle specific markers is also used in cases when cross-striation is absent. Muscle specific actin, desmin and myoglobin, as well as myogenic transcription factors myogenin and MyoD, have been used for diagnosis of RMS (30)(31)(32)(33)(34)(35)(36). The advantage of myogenin and MyoD is that they are expressed in the least differen tiated tumors, therefore they can be used as tumor markers for early diagnosis.…”