title: Expression of BAG-1 and BcL-2 proteins before and after neoadjuvant chemotherapy of locally advanced breast cancer.
abstract: 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.
authors.affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Box 424, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA. lpusztai@notes.mdacc.tmc.edu
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurti
authors.forename: Jorge
authors.initials: J
authors.lastname: Perez Cardona
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Marina
authors.initials: M
authors.lastname: Volchenok
authors.forename: Patricia
authors.initials: P
authors.lastname: Breitenfelder
authors.forename: Shu-Wan
authors.initials: SW
authors.lastname: Kau
authors.forename: Shin
authors.initials: S
authors.lastname: Takayama
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Krajewski
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis*; D016923:Cell Death; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014157:Transcription Factors; D016896:Treatment Outcome
chemical_list: C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D004317:Doxorubicin