Immunohistochemical Characterization of Sarcomas in Trp53+/− Haploinsufficient Mice

The use of immunohistochemical (IHC) staining in determining and/or confirming the cellular origin of poorly differentiated sarcomas was evaluated in this study. Sarcomatous neoplasms were evaluated in a research study conducted in 2 strains of p53+/− haploinsufficient mice. The most common neoplasms were undifferentiated sarcomas, followed by osteosarcomas and rhabdomyosarcomas (RMSs). The RMSs were poorly differentiated and appeared similar to the pleomorphic, or adult type, RMS of humans. All sarcomas stained positive by IHC for the mesenchymal cell intermediate filament vimentin. The RMSs were identified by positive IHC staining for myogenin, a transcription factor specific to skeletal muscle. Osteosarcomas were easily identifiable on hematoxylin and eosin–stained slides; no generally accepted IHC stain specific for bone is presently available. Some of the undifferentiated sarcomas contained numerous macrophages that stained positive for F4/80, a macrophage marker; the positive-staining cells were considered to be infiltrating macrophages. One-third of the neoplasms observed in this study were associated with subcutaneous implanted electronic microchips used for animal identification. Based upon histopathologic evaluation and IHC staining, it was not possible to distinguish neoplasms associated with subcutaneous microchips from neoplasms not associated with microchips.

[1]  T. Harada,et al.  Spontaneous extraskeletal osteosarcoma with various histological growth patterns in the abdominal wall of an ICR mouse , 2015, Journal of toxicologic pathology.

[2]  F. Okada,et al.  Inflammation-Related Carcinogenesis: Current Findings in Epidemiological Trends, Causes and Mechanisms , 2014, Yonago acta medica.

[3]  E. Chiocca,et al.  Cytomegalovirus infection leads to pleomorphic rhabdomyosarcomas in Trp53+/- mice. , 2012, Cancer research.

[4]  E. Monti,et al.  Rhabdomyosarcomas: an overview on the experimental animal models , 2012, Journal of cellular and molecular medicine.

[5]  J. Ward,et al.  Morphological and Immunohistochemical Characterization of Sarcomatous Tumors in Wild-Type and Genetically Engineered Mice , 2012, Veterinary pathology.

[6]  J. Sundberg,et al.  Rhabdomyosarcomas in Aging A/J Mice , 2011, PloS one.

[7]  F. Shimada,et al.  Extraskeletal Osteosarcoma with Pulmonary Metastasis in a Female F344 Rat , 2011, Journal of toxicologic pathology.

[8]  Julie A. Wilkins,et al.  p53 mutation and loss have different effects on tumourigenesis in a novel mouse model of pleomorphic rhabdomyosarcoma , 2010, The Journal of pathology.

[9]  J. Ward,et al.  The Histopathologic and Molecular Basis for the Diagnosis of Histiocytic Sarcoma and Histiocyte–Associated Lymphoma of Mice , 2010, Veterinary pathology.

[10]  B. Eyden Pleomorphic Rhabdomyosarcoma Showing Smooth-Muscle and Fibrohistiocytic Differentiation: A Single Case Report , 2010, Ultrastructural pathology.

[11]  F. Collin,et al.  Adult-type Rhabdomyosarcoma: Analysis of 57 Cases With Clinicopathologic Description, Identification of 3 Morphologic Patterns and Prognosis , 2009, The American journal of surgical pathology.

[12]  Alberto Mantovani,et al.  Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. , 2009, Carcinogenesis.

[13]  Toshimichi Yoshida,et al.  Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice , 2006, Oncogene.

[14]  W. Meyer,et al.  An Immunohistochemical Algorithm to Facilitate Diagnosis and Subtyping of Rhabdomyosarcoma: The Children's Oncology Group Experience , 2006, The American journal of surgical pathology.

[15]  M. Perron-Lepage,et al.  Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study to attempt to determine their histogenesis. , 2006, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[16]  N. Cordani,et al.  Malignant fibrous histiocytoma: a proposed cellular origin and identification of its characterizing gene transcripts. , 2003, International journal of oncology.

[17]  J. Coindre,et al.  Immunohistochemistry in the diagnosis of soft tissue tumours , 2003, Histopathology.

[18]  J. Haseman,et al.  The role of transgenic mouse models in carcinogen identification. , 2002, Environmental health perspectives.

[19]  P. Mann,et al.  The Trp53 Hemizygous Mouse in Pharmaceutical Development: Points to Consider for Pathologists , 2002, Toxicologic pathology.

[20]  T. Mentzel,et al.  Pleomorphic Rhabdomyosarcoma in Adults: A Clinicopathologic Study of 38 Cases with Emphasis on Morphologic Variants and Recent Skeletal Muscle-Specific Markers , 2001, Modern Pathology.

[21]  S G Lake,et al.  Tumors in long-term rat studies associated with microchip animal identification devices. , 2001, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[22]  Ricardo Ochoa,et al.  p53 +/- Hemizygous Knockout Mouse: Overview of Available Data , 2001, Toxicologic pathology.

[23]  R E Stoll,et al.  Transponder-Induced Sarcoma in the Heterozygous p53+/- Mouse , 1999, Toxicologic pathology.

[24]  H. Takahashi,et al.  Origin of histiocyte‐like cells and multinucleated giant cells in malignant fibrous histiocytoma: Neoplastic or reactive? , 1999, Pathology international.

[25]  J. Haseman,et al.  Spontaneous and Chemically Induced Proliferative Lesions in Tg.AC Transgenic and p53-Heterozygous Mice , 1998, Toxicologic pathology.

[26]  L Tomatis,et al.  Subcutaneous soft tissue tumours at the site of implanted microchips in mice. , 1997, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[27]  Kenneth H. Johnson,et al.  Foreign body tumorigenesis. , 1976, CRC critical reviews in toxicology.