Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients.
OBJECTIVE
The role of transforming growth factor beta (TGF-beta) in breast cancer is ambiguous; it can display both tumor suppressing and enhancing effects. Activation of the TGF-beta signal transduction system is subject to hormonal regulation. This study was conducted to further analyze the role of TGF-beta receptors in breast cancer and to evaluate their significance as prognostic markers.


METHODS
Expression of TGF-beta receptor I (TbetaRI) and TGFbeta receptor II (TbetaRII) was retrospectively analyzed by immunohistochemistry in 246 breast cancer patients.


RESULTS
Expression of TbetaRI was strongly correlated with tumor size (P < 0.001) and nodal status (P = 0.012) but only weakly with overall survival (P = 0.056). In contrast, TbetaRII was prognostic for overall survival in univariate analysis (P = 0.0370). In estrogen receptor (ER) -negative patients TbetaRII expression was correlated with highly reduced overall survival (P = 0.0083). In multivariate analysis TbetaRII proved to be an independent and highly significant prognostic marker with a hazard ratio of 6.8. Simultaneous loss of both ER and TbetaRII was associated with longer overall survival times comparable with those of ER-positive patients.


CONCLUSIONS
The results of this exploratory study show that TbetaRII is an independent, highly significant prognostic indicator for overall survival in ER-negative patients. In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGFbeta takes place, whereas tumor- promoting aspects remain intact.
Buck
Miriam B
MB
Robert Bosch Hospital, Department of Clinical Chemistry, Stuttgart, Germany.
Fritz
Peter
P
Dippon
Juergen
J
Zugmaier
Gerhard
G
Knabbe
Cornelius
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011960:Receptors, Estrogen / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D012189:Retrospective Studies; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II