Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma.
OBJECTIVE
Constitutive activation of JAK/STAT pathway is observed in various solid tumors and hematological malignancies. SOCS3 acts as a key negative regulator of JAK/STAT pathway and represents one of the candidate tumor suppressor genes. In the current study, we aimed to evaluate SOCS3 expression in breast carcinoma and to explore the prognostic significance of SOCS3.


METHODS
The expression of SOCS3 was measured by Western blot and immunohistochemistry in breast carcinoma cells and a large cohort of tissue microarray, respectively.


RESULTS
Among 367 human primary breast tumors, SOCS3 protein was detected in 103 patients. Deficient SOCS3 expression correlated significantly with lymph node metastasis (P = 0.003), blood vessel invasion (P = 0.029), VEGF (P = 0.001) and Ki-67 (P = 0.027). Univariate and multivariate analyses revealed that SOCS3 expression was an independent prognostic factor for disease-free survival (P < 0.0001). A positive SOCS3 protein expression correlated significantly with a low pSTAT3 protein expression in breast carcinoma (P = 0.015). The patients with a SOCS3 (+)/pSTAT3 (-) phenotype had a better prognosis than any other combination (DFI: P < 0.0001, BCSS: P = 0.013).


CONCLUSIONS
Deficient expression of SOCS3 is associated with an aggressive phenotype and portends a poor clinical outcome in breast carcinoma.
Ying
Mingzhen
M
Department of Oncology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai 200433, People's Republic of China.
Li
Dawei
D
Yang
Linjun
L
Wang
Mei
M
Wang
Ning
N
Chen
Ying
Y
He
Miaoxia
M
Wang
Yajie
Y
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis*
C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins