Increased invasiveness and aggressiveness in breast epithelia with cytoplasmic p63 expression.
Our previous studies revealed that pregnancy associated breast cancer (PABC) had significantly reduced nuclear p63 expression in myoepithelia, while intense cytoplasmic p63 expression in associated epithelia. Our current study assessed these epithelia using immunohistochemistry with a panel of aggressiveness and invasiveness related markers and comparative genomic hybridization (array-CGH) with over 30,000 DNA probes. These epithelia showed several unique alterations, including (1) immunohistochemical and morphological resemblance to invasive cancer, (2) significant gain in copy numbers of DNA coding genes for morphogenesis, angiogenesis, and metastasis, and (3) significant loss in copy numbers of DNA coding genes for tumor suppressors, cell adhesion, and macromolecular complex assembly or intra-cellular trafficking. Detected array-CGH alterations correlated well with in vivo expression of a number of corresponding proteins tested. These findings suggest that aberrant sub-cellular localization of p63 expression in normal or hyperplastic appearing epithelial cells may significant contribute to increased invasiveness and aggressiveness of these cells.
Hsiao
Yi-Hsuan
YH
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Su
Yan A
YA
Tsai
Horng-Der
HD
Mason
Jeffrey T
JT
Chou
Ming-Chih
MC
Man
Yan-gao
YG
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D003593:Cytoplasm / Q000378:metabolism*; D056915:DNA Copy Number Variations; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins