title: High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer.
abstract: Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebok
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Melike
authors.initials: M
authors.lastname: Öztürk
authors.affiliation: Department of Gynecology, Hospital Itzehoe, D-25524 Itzehoe, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heilenkötter
authors.affiliation: Department of Gynecology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Jaenicke
authors.affiliation: Department of Gynecology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Gynecology, Hospital Pinneberg, D-25421 Pinneberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Paluchowski
authors.affiliation: Department of Gynecology, Hospital Pinneberg, D-25421 Pinneberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Geist
authors.affiliation: Department of Gynecology, Hospital Elmshorn, D-25337 Elmshorn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Eicke
authors.initials: E
authors.lastname: Burandt
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Lebeau
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg - Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
keywords: breast cancer; class III β-tubulin; immunohistochemistry