TY - JOUR
T1 - Expression of BAG-1 and Bcl-2 proteins before and after neoadjuvant chemotherapy of locally advanced breast cancer
AU - Pusztai, Lajos
AU - Krishnamurti, Savitri
AU - Cardona, Jorge Perez
AU - Sneige, Nour
AU - Esteva, Francisco J.
AU - Volchenok, Marina
AU - Breitenfelder, Patricia
AU - Kau, Shu Wan
AU - Takayama, Shin
AU - Krajewski, Stanislaw
AU - Reed, John C.
AU - Bast, Robert C.
AU - Hortobagyi, Gabriel N.
N1 - Funding Information:
Development of the BAG-1 antibody was supported by funds to JCR from the NIH (CA-67329), The Susan G. Komen Foundation (9527) and also Global Medical Products Inc. Supported in part by grant no. K23-CA82119 from the National Cancer Institute (FJE).
PY - 2004
Y1 - 2004
N2 - It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p=0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.
AB - It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p=0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.
KW - Apoptosis
KW - BAG-1
KW - Bcl-2
KW - Chemosensitivity
KW - Preoperative chemotherapy
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U2 - 10.1081/CNV-120030213
DO - 10.1081/CNV-120030213
M3 - Article
C2 - 15199607
AN - SCOPUS:2342618469
SN - 0735-7907
VL - 22
SP - 248
EP - 256
JO - Cancer Investigation
JF - Cancer Investigation
IS - 2
ER -