Abstract. This study aimed to assess the pre-operative chemo- therapy impact on the relationship between estrogen receptor (ER) expression and markers of proliferation and apoptosis in primary and metastatic breast cancer. Immunohistochemical examinations were conducted on surgically removed ductal 

This study aimed to assess the pre-operative chemotherapy impact on the relationship between estrogen receptor (ER) expression and markers of proliferation and apoptosis in primary and metastatic breast cancer. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases in 135 patients. A total of 64 patients from this group underwent pre-operative chemotherapy and in 71 cases the surgery was performed without primary chemotherapy. A negative correlation between ERα and Ki-67 was found in primary tumors and lymph node metastases. A positive correlation was observed between ERα and Bcl-2. A positive correlation was also noted between ERβ and Bak, suggesting that the two ERs were involved in the regulation of proteins responsible for the control of the apoptotic process. Assessment of the expression of the proteins conducted separately in primary tumors and lymph node metastases did not reveal a significant effect of pre-operative chemotherapy on the correlations of ERs with Ki-67, Bcl-2 and Bak. However, the analysis of the correlations between the receptor expression in primary tumors and Ki-67, Bcl-2 and Bak in lymph node metastases showed a statistically significant impact of pre-operative chemotherapy on the correlations of ERα and Bcl-2 with ERβ and Bak, confirming involvement of the two ERs in the regulation of apoptosis during breast carcinogenesis. Introduction Estrogens play a key role in the development of breast cancer as they stimulate neoplastic cell proliferation. This proliferative effect occurs due to the induction of enzymes involved in nucleic acid synthesis, oncogene activation, as well as an increased production of various growth factors (1,2). The effectiveness of hormonal therapies in breast cancer treatment depends mostly on the status of estrogen receptors (ERs). Typical hormonal therapies, including ER selective modulators, aromatase inhibitors and ovarectomy, inhibit estrogen activity. Hormonal therapy is used in different stages of cancer progression. However, only approximately 60% of breast cancers with a positive ER status respond to endocrine therapy (3). The molecular basis of this resistance remains unclear. A plausible reason is the disturbance of the ERα/ERβ physiological relationship in primary breast cancer, or the dominant expression of one of the ER isoforms (4,5). Numerous studies have suggested that ERα-positive neoplasms develop mechanisms of growth and survival that are independent of ERs, such as through the overexpression of growth factors or their receptors, or changes in the proportions of proapoptotic and antiapoptotic proteins (6-12). Breast cancer development and progression depends on the survival chances of genetically modified cells. The range of factors that stimulate and inhibit the processes of proliferation and apoptosis determine survival chances of neoplastic cells in primary tumor and metastatic foci (13,14). However, despite intensive studies regarding ER expression and markers of proliferation and apoptosis in primary breast cancer, relatively little is known about the expression of these markers in metastatic foci, the main target of antineoplastic therapy. In previous studies, it was shown that pre-operative chemotherapy in breast cancer affects the expression of ERs and proteins involved in the processes of proliferation and apoptosis (15,16). The present study aimed to assess the impact of pre-operative chemotherapy on the correlation of ER expression with Ki-67, Bcl-2 and Bak in the primary tumor of breast cancer and in axillary lymph node metastases. ERα and ERβ expression in correlation with Ki-67, Bcl-2 and Bak in primary tumors and lymph node metastases of breast cancer: The effect of pre-operative chemotherapy LuIzA KANCzuGA-KOdA1,2,3, MARIuSz KOdA1,2,3, jAKuB TOMASzEwSKI1,2,3, KATARzYNA jARzABEK4, jOANNA LOTOwSKA1,2,3, MAREK BALTAzIAK1,2,3, uRSzuLA SuLKOwSKA1,2,3, MARIA SOBANIEC-LOTOwSKA1,2,3 and STaniSław SulkowSki1,2,3 1department of Pathology, Maria Sklodowska-Curie Memorial Bialystok Oncology Center, 15-027 Bialystok; 2jedrzej Sniadecki Memorial Hospital, 15-950 Bialystok; departments of 3General Pathomorphology, and 4Gynaecological Endocrinology, Medical university of Bialystok, 15-269 Bialystok, Poland Received May 26, 2010; Accepted September 2, 2010 dOI: 10.3892/ol.2010. 178 Correspondence to: Professor Stanislaw Sulkowski, department of General Pathomorphology, Medical university of Bialystok, waszyngtona 13, 15-269 Bialystok, Poland E-mail: sulek@zeus.amb. edu.pl