Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women.
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.
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.
Janice B
JB
Harvey
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA osbornet@niehs.nih.gov.
Tanasa S
TS
Osborne
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Hue-Hua L
HH
Hong
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Sachin
S
Bhusari
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Tai-Vu
TV
Ton
Experimental Pathology Laboratories, Research Triangle Park, North Carolina, USA.
Arun R
AR
Pandiri
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Tiwanda
T
Masinde
Experimental Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
June
J
Dunnick
Biostatistics Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Shyamal
S
Peddada
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Susan
S
Elmore
Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Current address: In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Mark J
MJ
Hoenerhoff
D000818:Animals; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation / Q000235:genetics*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D014599:Uterus / Q000737:chemistry / Q000473:pathology
D011075:Polybrominated Biphenyls; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C020806:tetrabromobisphenol A
Ccnd1; Cdh1; Ctnnb1; Her2; Kras; Tp53; Wistar Han rats; dometrial carcinoma; tetrabromobisphenol A