The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors and lymph node metastases of breast cancer.
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.
Koda
Mariusz
M
Department of General Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland.
Sulkowska
Mariola
M
Kanczuga-Koda
Luiza
L
Tomaszewski
Jakub
J
Kucharczuk
Waldemar
W
Lesniewicz
Tomasz
T
Cymek
Slawomir
S
Sulkowski
Stanislaw
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011300:Preoperative Care; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*
C494772:BAK1 protein, human; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate