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

Abstract

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 prolactinpositive 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 (ERa)-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 ERa-positive mammary tumors opens intriguing possibilities concerning the role of ERa cytoplasmic localization during EMT tumorigenesis.

Characterization of Spontaneous Mammary Tumors in Domestic Djungarian Hamsters (Phodopus sungorus)

“…Therefore, some researchers refer to these murine mammary carcinosarcomas as EMT-phenotype tumors. 2,5,18 Similarly, in these 7 cases of Djungarian hamsters, we recognized features indicating a transition from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells. In addition, polygonal cells exhibited an intermediate immunophenotype (CK(þ)/vimentin(þ)) between that of the epithelial and mesenchymal immunophenotypes.…”

“…26,27,29 Therefore, most classic carcinosarcomas that arise from various human organs are currently renamed as sarcomatoid carcinoma, undifferentiated (anaplastic) carcinoma, pleomorphic carcinoma, metaplastic carcinoma, or spindle cell carcinoma. 4,13,27,29 Similar terminological changes have also been suggested for mouse mammary carcinosarcomas, 2,5,18 as genetically engineered mice develop mammary carcinosarcomas with areas of epithelial to spindle cell transition. The morphology is reminiscent of the epithelial-mesenchymal transition (EMT), which occurs during embryonic development.…”

Stat1 is a suppressor of ErbB2/Neu-mediated cellular transformation and mouse mammary gland tumor formation

“…8C and D). 43,44 Both the nodular and papillary tumors do not stain for progesterone receptor (PR) (data not shown). and laminin can act as signaling molecules to epithelial cells, and stromal cells have been shown to promote epithelial cell growth by producing soluble growth stimulatory or inhibitory factors.…”

Pathobiology of Aging Mice and GEM

“…Proliferative mammary lesions and proliferative, often prolactin-secreting, pituitary lesions may be especially significant when FVB/N is used as a background strain in models of mammary neoplasia. 170,179,234 FVB/N mice are expected to be blind by about the time of weaning, with genetically determined retinal degeneration due to homozygosity for the rd1 mutation in the Pde6b Findings from multiple studies are summarized for each strain family. Supplemental Table S1 includes the references, substrain information (when reported), and original terminology.…”