The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study.
BACKGROUND
We recently found that DNA methylation of S100A2, spleen tyrosine kinase (SYK), and Stathmin-1 (STMN1) correlates with response to tamoxifen therapy in metastatic breast cancer. In this retrospective study, we investigated immunohistochemically whether these three markers are predictors of relapse in early breast cancer (EBC) patients treated with adjuvant tamoxifen alone.


METHODS
Immunohistochemical staining was performed for S100A2, SYK and STMN1 on a tissue microarray containing ER-positive invasive breast carcinomas from a study cohort of 215 operable breast cancer patients, who underwent radical local therapy and who were treated with adjuvant tamoxifen monotherapy. Cox regression was used to correlate staining intensity of the three markers with main endpoints in our study; disease-free survival (DFS), and disease-specific survival (DSS).


RESULTS
In univariate analysis, only STMN1 staining intensity strongly correlated with DFS (P = 0.014) and DSS (P = 0.002). In the groups of low and high STMN1 intensity, DFS was 84% and 63%, and DSS was 89% and 70%. STMN1 retained its prognostic value for DFS (P = 0.002) and DSS (<0.001) in the multivariate model together with lymph node status. We found also a trend to better DFS in patients with low STMN1 intensity in both lymph node-positive (P = 0.001) and -negative patients (P = 0.065). As the tumour cells did not express S100A2 (except in one case) the potential prognostic value of this marker was not evaluated.


CONCLUSIONS
Staining intensity of STMN1, but not SYK, predicted outcome in our collective of ER- positive tamoxifen treated EBC patients.
Golouh
Rastko
R
Institute of Oncology, Ljubljana, Slovenia.
Cufer
Tanja
T
Sadikov
Aleksander
A
Nussdorfer
Petra
P
Usher
Pernille Autzen
PA
Brünner
Nils
N
Schmitt
Manfred
M
Lesche
Ralf
R
Maier
Sabine
S
Timmermans
Mieke
M
Foekens
John A
JA
Martens
John W M
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002630:Chemotactic Factors / Q000096:biosynthesis*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000378:metabolism*; D009418:S100 Proteins / Q000096:biosynthesis*; D050777:Stathmin / Q000096:biosynthesis*; D000072377:Syk Kinase; D013629:Tamoxifen / Q000627:therapeutic use*
D002630:Chemotactic Factors; D047908:Intracellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; D009418:S100 Proteins; C098997:S100A2 protein, human; C493995:STMN1 protein, human; D050777:Stathmin; D013629:Tamoxifen; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase