Steroid Sulfatase Expression In Cancerous, And In Normal, Human Breast Tissues And Its Role In The Pathogenesis And Development Of Breast Carcinoma

Objective: Hormonal treatment has become one of the major therapies in breast cancer, but only 33-50% of human breast cancers respond to hormonal treatment. One such mechanism of treatment failure could be the high concentration of estrogens in the tumor. Local biosynthesis of estrogens are believed to play a very important role in the high concentration of estrogen in breast carcinoma, and may be more important than circulating estrogens on the development of breast cancer. Steroid sulfatase(STS) is one of key enzymes involved in the local synthesis of estrogen, and may be a new target for the endocrine therapy of breast cancer. We have tested STS mRNA and protein levels in breast cancer and normal breast tissues, and analyzed the relationship of STS expression level with patients'age, menopausal status, and clinicopathologic characteristics, to find its role in pathogenesis and development of breast carcinoma, and as a new target for hormonal treatment.Methods:Forty paired specimens of breast tumor and the tissue, which at least 5cm away from the tumor, were obtain from patients who underwent mastectomy and none of whom have a history of radiotherapy, chemotherapy or hormonal therapy. All tumors were pathologically diagnosed as breast carcinoma, and the tissues away from the tumor were pathologically diagnosed as normal breast. The expression of STS mRNA and protein, in breast cancer and normal breast tissues, were examined by reverse transcription-polymerase chain reaction and immunohistochemistry. STS expression level in breast cancer and normal breast tissues was analyzed and analyzed according to clinicopathologic characteristics, such as age, menopausal status, tumor size, lymph node status, pathologic staging, estrogen receptor(ER), progesterone receptor(PR),human epidermal growth factor receptor number 2(Her-2),et al.Results:1 STS mRNA was detected in 27/40(67.5%) of breast cancer tissue and in 22/40(55%) of normal breast tissue. The level of STS mRNA in breast cancer tissue was 0.4034, 0.2225～0.5844(mean, 95% confidence interval); in normal breast tissue the value was 0.4208, 0.2203～0.6214. There was no significant difference between breast cancer and normal breast tissue on STS mRNA expression level (P=0.669).2 STS immunoreactivity was mainly detected in the cytoplasm of carcinoma cells and epithelial cells in normal glands, but not detected in the stroma. Only in three patients it was detected in the nucleus of carcinoma cells, the pathological types including invasive ductal carcinoma, invasive lobular carcinoma, and invasive micropapillary carcinoma. STS immunoreactivity was not detected in the nucleus of normal epithelial cells. The positive expression of STS in breast cancer tissue was 70.0% , with 40.0% showing 1+, 20.0% 2+ and 10.0% 3+, and negative expression rate was 30.0%. The positive expression of STS in normal breast tissue was 42.5%, with 22.5% showing 1+, 15.0% 2+ and 5.0% 3+, and negative expression rate was 57.5%. STS immunoreactivity was significantly higher in breast cancer tissues than in normal breast tissues (P=0.028).3 In both tissues, STS immunoreactivity was correlated positively with mRNA expression level. (in breast cancer tissues Rs=0.564, P<0.001;in normal breast tissues Rs=0.382,P= 0.015).4 No correlation could be seen between patients'age and STS mRNA/protein expression level in breast cancer tissues or in normal breast tissues.5 Stratified analysis showed that the higher STS immunoreactivity in breast cancer tissues than in normal breast tissues, was mainly in premenopausal patients and in the advanced stage of the disease. In premenopausal patients, STS immunoreactivity was higher in breast cancer tissues than in normal breast tissues (P=0.049). In the tumor>2cm group, it was higher in breast cancer tissues than in normal breast tissues(P=0.037). In the lymph node positive patients, it was higher in breast cancers tissues than in normal breast tissues (P=0.004). In stageⅡ/Ⅲ, it was higher in breast cancer tissues than in normal breast tissues (P=0.014). The STS immunoreactivity, between breast cancer tissues and normal breast tissues, could not be seen significant differences in the postmenopausal group, tumor≤2.0cm group, lymph node negative group, nor in stageⅠgroup. No significant differences could be seen on STS mRNA expression level in any groups .6 In breast cancer tissues, there were no significant differences of STS expression level in different menopausal status or pathological characteristics There was no significant differences, on STS mRNA and protein expression level, between pre- and postmenopausal patients, invasive ductal carcinoma and invasive lobular carcinoma, tumor≤2.0cm and tumor>2cm patients, lymph node negative and positive patients, nor between stageⅠand stageⅡ/Ⅲpatients. In the breast cancer tissue, there was no significant relationship of STS mRNA/protein expression level with ER, PR, nor with Her-2. There was no significant difference, on STS mRNA/protein expression level, have been detected between positive and negative groups of each receptors.Conclusions: 1 STS immunoreactivity was mainly detected in the cytoplasm of carcinoma cells and epithelial cells in normal glands, but not in the stroma. We have found it could be detected in the nucleus of carcinoma cells in a few breast cancer tissues2 The STS immunoreactivity was higher in breast cancer tissue than in normal breast tissue, but mRNA expression level did not have significant differents between the two tisses. The higher immunoreactivity in breast cancer tissue than in normal breast tissue was mainly in premenopausal patients and in the advanced stage of the disease.3 STS mRNA expressing level was significant correlated with its immunoreactivity, in breast cancer and normal breast tissues.4 In breast cancer tissue, there was no significant relationship of STS mRNA/protein expression level with ER, PR, nor with Her-2. There was no significant difference, on STS mRNA expression level or protein expression rate, have been detected between positive and negative groups of each receptors.