Estrogen-regulated proteins cathepsin D and pS2 in breast carcinoma

In addition to classical prognostic/predictive factors, significant biological markers have been identified to provide potentially relevant information regarding natural or clinical course of breast cancer. Steroid receptor status of the primary breast cancer have been proven to be a predictor of response to endocrine therapy since up to 80 % of patients with steroid receptor-positive tumors respond to endocrine treatment. In order to improve the predictive value of steroid receptor status, attention has been paid to estrogen-regulated proteins, including pS2 and cathepsin D among others that may be indicators of a functional signal transduction pathway through which tumor cells respond to estrogen stimulation. It has been shown that pS2 protein may be constitutive product as well as estrogen-regulated product in breast carcinoma. pS2 appears to be positively correlated with ER, associated with a good prognosis and a predictor of response to endocrine treatment of primary and metastatic breast cancer. The expression cathepsin D may be both constitutive and overexpressed as a result of estrogen-induced transcription. It was believed that the main role of cathepsin D was to degrade protein, but many other biological functions of cathepsin D were recognized. Cathepsin D level in primary breast cancer has been demonstrated as an independent marker of poor prognosis associated with increased risk for metastasis and shorter survival times. Our recent results show direct correlation of cathepsin D positivity with pS2 expression. Additionally, we found that cathepsin D is statistically significantly associated with pS2 both in node-negative and node-positive patients bearing tumors smaller than 2 cm.