Prognostic significance of TGFbeta-1 and pSmad2/3 in breast cancer patients with T1-2,N0 tumours.
BACKGROUND
The transforming growth factor beta (TGFbeta) signaling pathway has been shown to exert divergent effects and to cross-talk with estrogen pathways in mammary gland tumorigenesis. TGF signaling in early stage breast cancer was investigated by examining the expression of TGFbeta-1 and the signaling mediators pSmad2/3 and Smad4. Their association with oestrogen and progesterone receptors, as well as with clinical and pathological features was also analyzed.


METHODS
Sixty-one tumor specimens from surgically treated patients with primary T12,N0 breast cancer were examined. The expression of TGFbeta-1, pSmad2 and Smad4 was assessed implementing immunohistochemical assays.


RESULTS
TGFbeta-I, pSmad2/3 and Smad4 were expressed in 50.9%, 74.0% and 61.0% of specimens, respectively. The degree of expression of the three molecules was significantly associated with each other. Loss of pSmad2/3 expression indicated a shorter disease-free survival in all patients, including those with oestrogen receptor-positive tumors. Patients not expressing TGFbeta-1 were 4.6 times more likely to experience distant recurrence.


CONCLUSIONS
Our results demonstrate that pSmad2/3 and TGFP-1 may be promising novel prognostic markers for T1.2,N0 breast carcinomas.
Koumoundourou
Dimitra
D
Department of Pathology, University of Patras Medical School, Patras, Greece.
Kassimatis
Theodoros
T
Zolota
Vasiliki
V
Tzorakoeleftherakis
Evangelos
E
Ravazoula
Panagiota
P
Vassiliou
Vassilios
V
Kardamakis
Dimitrios
D
Varakis
John
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000096:biosynthesis* / Q000378:metabolism; D051900:Smad3 Protein / Q000096:biosynthesis* / Q000378:metabolism; D051901:Smad4 Protein / Q000096:biosynthesis / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1