Histopathological Features of Mouse Models of Embryonal Rhabdomyosarcoma
DP Schuetze, K Nishijo, LD Hampton, AT McCleish, C Keller, BP Rubin. Cleveland Clinic, Cleveland, OH; University of Texas Health Science Center, San Antonio, TX
Background: Embryonal rhabdomyosarcoma (ERMS) is a rare tumor that occurs predominantly in children. We have developed a set of conditional mouse models of ERMS to understand the cell of origin and provide a preclinical platform for testing new therapies.
Design: Conditional mouse models of ERMS were developed using Cre:loxP and targeted knock-in technology. This model utilizes satellite cell, myoblast or myofiber-specific expression of Cre recombinase to delete combinations of Ptch, p53, and/or Rb, tumor supressors associated with human ERMS. Seventy-six lesions were examined with hematoxylin and eosin and also trichrome. Immunohistochemical studies for desmin and myogenin (and MyoD1 for several cases) were performed. The general histologic features were described and rhabdomyoblasts, cross striations, and reactivity for desmin, myogenin, and MyoD1 were noted. A histologic classification was rendered for each case.
Results: Seventy six tumors were classified. Thirty-one (41%) were classified as ERMS. Features common to these cases included fascicles of spindle cells with eosinophilic cytoplasm, cytoplasmic reactivity with desmin (29/29 tested cases, 100%), and nuclear reactivity with myogenin (22/27 tested cases, 81.5%) and/or MyoD1 (4/5 tested cases, 80%). A majority of cases (18/31; 58%) contained rhabdomyoblasts. Cross striations occurred in 13/31 (42%). Other subtypes of rhabdomyosarcoma (RMS) were seen, including 4 cases of alveolar RMS and 2 cases of pleomorphic RMS. Eleven tumors were classified as spindle cell sarcoma with possible myogenic differentiation, as histologic and/or immunophenotypic criteria of unequivocal ERMS were not met. Other malignancies occurred, including 4 cases of osteosarcoma, 9 cases of spindle cell sarcoma, not otherwise specified, 1 case of malignant epithelioid neoplasm, not otherwise specified, and 3 cases of lymphoma.
Conclusions: These conditional mouse models of ERMS generate tumors with histologic and immunophenotypic characteristics similar to those seen in human ERMS in approximately 41% of the lesions. Since not all lesions that develop are ERMS, histopathological examination will play a crucial role in studies involving these models. The continuity between spindle cell sarcomas and ERMS for some models suggests that certain myogenic cells of origin can give rise to a spectrum of poorly vs well differentiated tumors.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 229, Wednesday Morning