title: Hormone Receptor Expression in Spontaneous Uterine Adenocarcinoma in Fischer 344 Rats.
abstract: Most uterine cancers, the most common gynecological malignancies in women in developed countries, are hormone-dependent endometrial adenocarcinomas (EACs) that express estrogen and progesterone receptors. Although rat strains exist with a high spontaneous incidence of EAC, the Fischer 344 (F344) strain, previously one of the most commonly used strains in carcinogenicity testing, is not a high-incidence strain. To better understand the biology of this neoplasm, we assessed estrogen receptor α (ER), progesterone receptor (PR), and Ki-67 expression using immunohistochemistry in spontaneous EAC in 18 F344 rats used as control animals in 2-year National Toxicology Program bioassays. Of the 18 tumors, 9 were well-differentiated and 9 were poorly differentiated. Most tumors, 7/18, were ER+PR+, as observed in women. Of the remainder, 6/18 were ER+PR-, 2/18 were ER-PR+, and 3/18 were ER-PR-. Well-differentiated tumors were ER+ (8/9) more often than poorly differentiated tumors (5/9). The percentage of ER+ tumors (72%) in rats was similar to that seen in women, but rats less frequently had PR+ (50%) tumors than women. The heterogeneous estrogen and progesterone receptor immunophenotypes observed in F344 rats in this study highlight the importance of evaluating hormone receptor expression in animal models used for chemical evaluations.
authors.affiliation: Integrated Laboratory Systems, Inc., Research Triangle Park, North Carolina, USA.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Willson
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Herbert
authors.affiliation: Department of Pathology/Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA jmcline@wakehealth.edu.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone
keywords: F344 rats; endometrial adenocarcinoma; estrogen receptor; progesterone receptor; uterine neoplasms.