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

Prolactin-secreting pituitary adenomas are common spontaneous lesions in ageing 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 ageing wild type FVB/N females to establish the prevalence and the nature of spontaneous mammary and pituitary tumors. Tissues from mammary and pituitary gland 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 immunohistochemisty 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 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 progesteron 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 to previous reports, prolactinoma-associated-mammary tumors displayed a broader morphological spectrum including cases with EMT-phenotype. The high prevalence of ERα-positivity in prolactinoma-associated mammary tumors opens intriguing possibilities concerning the role of ERα cytoplasmic localization during EMT-tumorigenesis.