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Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women. 2015

Janice B Harvey, and Tanasa S Osborne, and Hue-Hua L Hong, and Sachin Bhusari, and Tai-Vu Ton, and Arun R Pandiri, and Tiwanda Masinde, and June Dunnick, and Shyamal Peddada, and Susan Elmore, and Mark J Hoenerhoff
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

Endometrial carcinoma is the most common gynecologic malignancy is the United States and accounts for 6% of all cancers in women. The disease is classified as type I or type II based on clinicopathologic and molecular features. It is a multifactorial disease with a number of risk factors, including environmental exposures. How environmental exposures, such as flame retardants, may affect the incidence of endometrial cancer is a topic of current and ongoing interest. Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant found in a variety of household products. A recent 2-year National Toxicology Program carcinogenicity study found that exposure to TBBPA was associated with a marked increase in the development of uterine tumors, specifically uterine carcinomas, in Wistar Han rats. Molecularly, TBBPA-induced uterine carcinomas in Wistar Han rats were characterized by a marked increase in tumor protein 53 mutation compared to spontaneous uterine carcinomas, as well as overexpression of human epidermal growth factor receptor 2. Similar to spontaneous carcinomas, tumors in TBBPA-exposed rats were estrogen receptor-alpha positive and progesterone receptor negative by immunohistochemistry. The morphologic and molecular features of uterine carcinomas in TBBPA-exposed rats resemble those of high-grade type I tumors in women, and these data suggest that exposure to TBBPA may pose an increased cancer risk.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011075 Polybrominated Biphenyls Biphenyl compounds which are extensively brominated. Many of these compounds are toxic environmental pollutants. Polybromobiphenyl Compounds,Biphenyls, Polybrominated,Compounds, Polybromobiphenyl
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014594 Uterine Neoplasms Tumors or cancer of the UTERUS. Cancer of Uterus,Uterine Cancer,Cancer of the Uterus,Neoplasms, Uterine,Neoplasms, Uterus,Uterus Cancer,Uterus Neoplasms,Cancer, Uterine,Cancer, Uterus,Cancers, Uterine,Cancers, Uterus,Neoplasm, Uterine,Neoplasm, Uterus,Uterine Cancers,Uterine Neoplasm,Uterus Cancers,Uterus Neoplasm
D014599 Uterus The hollow thick-walled muscular organ in the female PELVIS. It consists of the fundus which is the site of EMBRYO IMPLANTATION and FETAL DEVELOPMENT. Beyond the isthmus at the perineal end of fundus, is CERVIX UTERI (the neck) opening into VAGINA. Beyond the isthmi at the upper abdominal end of fundus, are the FALLOPIAN TUBES. Fundus Uteri,Uteri,Uterine Cornua,Uterine Fundus,Uterus Cornua,Womb,Cornua, Uterine,Fundus Uterus,Fundus, Uterine,Uteri, Fundus,Wombs
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D016889 Endometrial Neoplasms Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells. Cancer of Endometrium,Endometrial Cancer,Endometrial Carcinoma,Cancer of the Endometrium,Carcinoma of Endometrium,Endometrium Cancer,Neoplasms, Endometrial,Cancer, Endometrial,Cancer, Endometrium,Cancers, Endometrial,Cancers, Endometrium,Carcinoma, Endometrial,Carcinomas, Endometrial,Endometrial Cancers,Endometrial Carcinomas,Endometrial Neoplasm,Endometrium Cancers,Endometrium Carcinoma,Endometrium Carcinomas,Neoplasm, Endometrial

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