Retro-differentiation of the liver in MMTV-neu (erbB-2) transgenic mice, bearing a mammary adenocarcinoma.

MMTV-neu transgenic adult mice develop mammary tumors metastatizing into the lungs and are a model for human breast cancer studies. We investigated the liver of these animals, knowing that it influences tumor growth and the host quality of life. The organ displayed features normally not present in the adult liver though hepatocytes looked uninjured. Hemopoietic stem cell (CD34+) infiltrates were abundant in sub-capsular and periportal sinusoids; endothelial cells were CD34+ only in these regions. Epsilon (embryonal) and gamma (fetal) chains of hemoglobin were expressed by some erythropoietic cells; erythroblasts were peroxidase positive and showed protoporphyrin autofluorescence. Myelopoietic clusters and thrombopoietic cells were also present. Hepatocytes in the sub-capsular region and in the limiting plate expressed AE1 (acid) and AE3 (basic) cytokeratins, vimentin and AFP, typical of hepatoblasts. Most hepatocytes expressed AFP. Portal tracts showed cellular overcrowding with many cells displaying “oval cell” morphology and AE1, AFP and CD34 expression. Production of fetal hemoglobin (suited for hypoxic tissue oxygenation) and of AFP (immunosuppressant) might be an index of adaptation to the tumor presence. Retro-differentiation with oval cell presence occur in liver regeneration but also in early liver carcinogenesis and thus need to be further investigated. (MURST and FAR funds)