Morphologically similar normal and hyperplastic mammary ductal cells associated with and without malignant lesions have a different immunohistochemical profile
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and George Washington University Medical Center, Washington, DC, United States
AIM: Our previous studies revealed that a subset of morphologically normal and hyperplastic mammary ductal cells in tissues of ductal carcinoma in situ (DCIS) shared several malignant features with their malignant counterparts (Man et al. Breast Cancer Res 5: R231-241, 2003). This study attempts to assess whether these cells are immunohistochemically different from normal and hyperplastic cells that are not associated with malignant lesions. METHODS: Consecutive sections at 4-5 um thickness were prepared from reduction mammoplasties with no cancer history, no mammographic and histological abnormalities, from regular ductal hyperplasia, and from DCIS (n=30 for each category) with simultaneous normal, hyperplastic, and neoplastic components. Sections were double immunostained for smooth muscle actin and Ki-67, plus a panel of markers that are reported to be exclusively or preferentially present in malignant cells. The structural integrity of the myoepithlial (ME) cell layers, the cell proliferation rate, and the expression status of those markers among cases were compared. RESULTS: Compared to their morphologically similar counterparts in reduction mammoplasties and regular ductal hyperplasia, clusters of non-malignant cells in nearly half of the DCIS cases displayed several unique features, which were shared by the malignant lesions: [1] A significantly higher frequency of focal ME cell layer disruptions; [2] A significantly higher rate of cell proliferation; [3] A significantly higher level of BP1 expression; [4] Over-expression of p53 and/or c-erb B2. These cell clusters were generally adjacent, while some were at a distance, to the malignant lesions. These cell clusters were architecturally and morphologically distinct from the malignant cells, whereas they were indistinguishable from the adjacent non-malignant cells in H & E stained sections. CONCLUSIONS: A subset of normal and hyperplastic ductal cells associated with malignant lesions might belong to a not yet defined malignant cell population.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 797 (Manifestations of cancer).