Mammary Tumor Phenotypes in Wild-Type Aging Female FVB/N Mice with Pituitary Prolactinomas

Abstract

Prolactin-secreting pituitary adenomas are common spontaneous lesions in aging FVB females. Prolactin-secreting pituitary proliferations play a significant role in mouse mammary tumorigenesis generally producing adenosquamous carcinomas. Since genetically engineered FVB mice are frequently used to study mammary tumor biology, we have examined a cohort of 64 aging wild-type FVB/N females to establish the prevalence and the nature of spontaneous mammary and pituitary tumors. Tissues from mammary and pituitary glands were studied by histopathology and immunohistochemistry. Of the 64 examined mice, 20 had pituitary tumors and 20 had mammary tumors. Mammary and pituitary tumors were associated in 17 mice. All pituitary tumors were prolactin-positive by immunohistochemistry and classified as prolactinomas. Fourteen mammary tumors, including 12 cases with and 2 without concurrent prolactinomas, were adenocarcinomas with different combinations of epithelial growth patterns. Five mice with prolactinomas had mammary tumors characterized by the epithelial-mesenchymal transition (EMT) phenotype. Estrogen receptor alpha (ERα)-positivity was observed for 14 of the 18 mammary tumors tested, including both adenocarcinomas with nuclear immunoreactivity and EMT-phenotype tumors with both nuclear and cytoplasmic immunoreactivity. No immunoreactivity for the progesterone receptor was observed. This study confirms that spontaneous prolactinomas and mammary tumors are both common and significantly associated lesions in FVB mice. Parity and age represented risk factors for the development of these tumors. Compared with previous reports, prolactinoma-associated mammary tumors displayed a broader morphologic spectrum, including cases with the EMT phenotype. The elevated number of prolactinoma-associated and ERα-positive mammary tumors opens intriguing possibilities concerning the role of ERα cytoplasmic localization during EMT tumorigenesis.