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Pathol Int. 1999 May;49(5):435-43.

Proliferative activity and tumor angiogenesis is closely correlated to stromal cellularity of fibroadenoma: proposal fibroadenoma, cellular variant.

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Pathology Division, National Cancer Center Research Institute East, Chiba, Kashiwa, Japan.


Fibroadenoma (FA) is the most common benign tumor of the breast in adult women. Some FA have a highly cellular stroma, making it difficult to differentiate from phyllodes tumors (PT). Forty-three FA were grouped into: (i) 27 conventional type (FACT) median stromal cellularity (SC) of highest cellular area (HCA), < or = 125 cells/1 high-power field (HPF); and (ii) 16 cellular variant (FACV) median SC of HCA, > 125 cells/1 HPF. These were studied for the proliferative activity of their stromal cells. Expression of c-fos, p53, basic fibroblast growth factor (bFGF), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor (VEGF) in the stromal cells were examined in the FA and 12 PT to determine whether it is possible to separate FACV from FACT. The proliferative activity of stromal cells was evaluated by the labeling index (LI) of proliferating cell nuclear antigen (PCNA). Conventional type fibroadenoma stromal cells had the lowest frequency of c-fos, p53, bFGF, FGFR and VEGF protein expression; PT stromal cells had the highest frequency of expression; and FACV stromal cells had an intermediate frequency of expression. Multivariate analysis demonstrated that bFGF and FGFR expression are significantly correlated with SC of FA. Separation of FACV from FACT by SC seems appropriate in revealing the phenotypic and biological differences of FA. The SC of FA seems to be regulated by bFGF and FGFR expression.

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