Cyclin D1, retinoblastoma, p53, and Her2/neu protein expression in preinvasive breast pathologies: Correlation with vascularity

Objectives: Preinvasive breast pathologies show a degree of vascularization that correlates with risk of invasion. Recently, numerous oncogenes and tu mor suppressor genes have been shown to regulate neovascularization. Theref ore, we examined archival tissues of preinvasive breast pathologies by immu nohistochemistry for alterations in the expression of four proteins, cyclin D1, retinoblastoma (Rb), p53, and Her2/neu, known to be important in breas t tumorgenesis, and correlated these data with tissue vascularity. Methods: Vascularity was determined by immunologic detection of von Willebrand fact or. For carcinoma in situ (CIS) both stromal vascularity (MVD) and vascular cuffing (MCD) were determined. Results: We found that cyclin D1 expression was increased in usual hyperplasia (11% of cases). Atypical hyperplasia, n oncomedo CIS and comedo CIS were positive in 43, 49, and 57% of cases, resp ectively. Changes in Rb and p53 were rare in hyperplasia but occurred in 8 and 10% of CIS, respectively. Her2/neu protein was identified rarely in aty pical hyperplasia and in both noncomedo and comedo ductal CIS. Neither Rb n or Her2/neu expression correlated with vascularity. p53 immunoreactivity co rrelated positively with both MCD and MVD. Cyclin D1 was negatively associa ted with MVD. Conclusion: These data suggest that p53 and cyclin D1 protein s may regulate the microvessel density of preinvasive breast pathologies. C opyright (C) 2001 S. Karger AG, Basel.