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.