Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade LPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.