title: alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies.
abstract: BACKGROUND
  alphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. The purpose of this study was to evaluate alphaB-crystallin with respect to clinicopathological parameters and the outcome of patients with operable high-risk breast cancer.
  
  
  METHODS
  A total of 940 tumors were examined, derived from an equal number of patients who had participated in two randomized clinical trials (paclitaxel-containing regimen in 793 cases). Immunohistochemistry for ER, PgR, HER2, Ki67, CK5, CK14, CK17, EGFR, alphaB-crystallin, BRCA1 and p53 was performed. BRCA1 mutation data were available in 89 cases.
  
  
  RESULTS
  alphaβ-crystallin was expressed in 170 cases (18.1%) and more frequently in triple-negative breast carcinomas (TNBC) (45% vs. 14.5% non-TNBC, p < 0.001). alphaB-crystallin protein expression was significantly associated with high Ki67 (Pearson chi-square test, p < 0.001), p53 (p = 0.002) and basal cytokeratin protein expression (p < 0.001), BRCA1 mutations (p = 0.045) and negative ER (p < 0.001) and PgR (p < 0.001). Its overexpression, defined as >30% positive neoplastic cells, was associated with adverse overall survival (Wald's p = 0.046). However, alphaB-crystallin was not an independent prognostic factor upon multivariate analysis. No interaction between taxane-based therapy and aβ-crystallin expression was observed.
  
  
  CONCLUSIONS
  In operable high-risk breast cancer, alphaB-crystallin protein expression is associated with poor prognostic features indicating aggressive tumor behavior, but it does not seem to have an independent impact on patient survival or to interfere with taxane-based therapy.
  
  
  BACKGROUND
  ACTRN12611000506998 (HE10/97 trial) and ACTRN12609001036202 (HE10/00 trial).
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Triantafyllia
authors.initials: T
authors.lastname: Koletsa
authors.affiliation: Third Department of Medical Oncology, "Hygeia" Hospital, Athens, Greece.
authors.forename: Flora
authors.initials: F
authors.lastname: Stavridi
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kostopoulos
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, University Campus, 54124 Thessaloniki, Greece ; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.affiliation: Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Eleftheraki
authors.affiliation: Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research NCSR Demokritos, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Konstantopoulou
authors.affiliation: Department of Clinical Therapeutics, "Alexandra" Hospital, University of Athens School of Medicine, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.affiliation: Department of Pathology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.affiliation: First Department of Medicine, "Laiko" General Hospital, University of Athens, Medical School, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.affiliation: Department of Medicine, Division of Oncology, University Hospital, University of Patras Medical School, Patras, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.affiliation: Second Department of Medical Oncology, "Metropolitan" Hospital, Piraeus, Greece.
authors.forename: Dimosthenis V
authors.initials: DV
authors.lastname: Skarlos
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.affiliation: Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efstratiou
authors.affiliation: Second Department of Internal Medicine, Oncology Section, "Hippokration" Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
keywords: AlphaB-crystallin; BRCA gene mutations; Basal core phenotype; Breast cancer; Taxane-based therapy; Triple-negative breast cancer