Favorable prognostic value of SOCS2 and IGF-I in breast cancer.
BACKGROUND
Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer.


METHODS
We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry.


RESULTS
SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 - 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 - 0.388, P = 0.002).


CONCLUSIONS
This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors.
Haffner
Michael C
MC
Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. Michael.Haffner@i-med.ac.at <Michael.Haffner@i-med.ac.at>
Petridou
Barbara
B
Peyrat
Jean Phillipe
JP
Révillion
Françoise
F
Müller-Holzner
Elisabeth
E
Daxenbichler
Günter
G
Marth
Christian
C
Doppler
Wolfgang
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019556:COS Cells; D044584:Carcinoma, Ductal / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis* / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection
C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D007334:Insulin-Like Growth Factor I