The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors and lymph node metastases of breast cancer

Abstract

The aim of this study was the analysis of Ki-67, Bcl-2 and Bak expression in primary tumor and axillary lymph node metastases of breast cancer as well as an attempt to assess preoperative chemotherapy influence on the mentioned markers with regard to changes in the morphological appearance of the primary tumor and its metastases. Immunohistochemical examinations of Ki-67, Bcl-2 and Bak expression were conducted on sections collected from 135 patients treated surgically on invasive ductal breast cancer. Sixty-four of these patients were administered preoperative chemotherapy, whilst on 71 patients the surgery was performed without initial chemotherapy. In the group of patients without preoperative chemotherapy positive correlation in Ki-67 and Bcl-2 expression between primary tumors and lymph node metastases (p<0.0001, r=0.707; p<0.0001, r=0.604, respectively) was observed. In the group of patients after chemotherapy positive correlation between primary tumors and lymph node metastases in case of Bcl-2 and Bak proteins (p<0.04, r=0.424; p<0.02, r=0.478, respectively) was observed. It was also found that preoperative chemotherapy has an influence on the expression of proteins connected with proliferation and apoptosis and thus, it can influence neoplastic process biology. It does not have any significant impact on the proapoptotic Bak protein expression either in primary tumor or in lymph node metastases of breast cancer. However, it is related to lower expression of antiapoptotic Bcl-2 protein (p<0.0005) and of Ki-67 proliferation marker (p<0.03) in primary tumors, which indirectly indicates a beneficial influence of preoperative chemotherapy on the primary tumor. Concurrently, the influence of neoadjuvant therapy on lymph node metastases seems to be relatively small, which can limit its effectiveness.

High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)‐positive breast cancer

“…ER, PgR, HER2 and Ki67 status were available allowing determination of the tumour subtype, 46% (165) of patients had Luminal A disease (ER or PgR-positive, HER2-negative and low Ki67 <14%), 22% (81) had Luminal B disease (ER-or PgR-and HER2-positive or ER, PgR and high Ki67 (>14%)), 20% (72) had triple negative disease (ER-, PgR-and HER2-negative) and 10% (38) had HER2 enriched (ER-and PgR-negative, HER2-positive).…”

“…are associated with prognosis and or response to therapy in breast cancer [37][38][39] . Figure 3C and also for the cells used in the wst-1 assays Figure 4A.…”

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

“…Previously, we showed that pre-operative chemotherapy affects breast cancer metastases to lymph nodes to a considerably lesser degree as compared to primary tumors. In the case of significant damage to the primary tumor, followed by an inability to determine ER expression, we demonstrated that tumor assessment may successfully be performed by means of metastases to local lymph nodes (15,16). Although pre-operative chemotherapy did not significantly affect ER expression in the primary tumor, we observed its impact on the expression of proteins correlated with proliferation and apoptosis; therefore, it influences neoplastic process biology.…”

“…As previously described (15,16), the proteins studied were not visualized due to substantial damage to primary tumor cells in 19 of the patients that underwent chemotherapy. Therefore, further analyses, including statistical evaluation, were performed in the group of 45 female patients with invasive ductal breast cancer, in which immunohistochemical evaluation of the markers examined was feasible despite preoperative chemotherapy.…”

“…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.…”