p-STAT3 expression in breast cancer correlates negatively with tumor size and HER2 status

Abstract

Although some studies have reported the expression and clinical significance of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in breast cancer tissues, it is still controversial whether p-STAT3 play a role in promoting or suppressing cancer. Here, we used immunohistochemistry analysis to explore expression of p-STAT3 in 407 cases of breast cancer, and analyzed the relationship between p-STAT3 expression and the clinicopathological characteristics and prognosis of breast cancer patients. Positive p-STAT3 expression was seen in 112 cases (27.5%) of breast cancer. p-STAT3 expression was negatively correlated with tumor size, tumor stage and human epidermal growth factor receptor 2 (HER2) status, and the positive rate of p-STAT3 was lowest in HER2-enriched subtype breast cancer (15.3%), while other subtypes were luminal B (23.0%), luminal A (30.2%), and triple-negative breast cancer (TNBC) (37.5%). Logistic regression model multivariate analysis showed that the independent correlation factor of p-STAT3 expression in breast cancer was tumor size (OR = 0.187, 95% CI = 0.042–0.839, P = .029) and HER2 status (OR = 0.392, 95% CI = 0.216–0.710, P = .002). In this study, no clear relationship was observed between patients’ prognosis and expression of p-STAT3. Therefore, we suggest that p-STAT3 expression in breast cancer is negatively correlated with tumor size and HER2 status, but appears to have no effect on survival.

STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential

“…There is conflicting evidence regarding the prognostic value of STAT3 mRNA expression or immunostaining of phosphorylated STAT3 (phospho-STAT3), marking transcriptionally active STAT3. Positive phospho-STAT3 (Y705) expression is highest in TNBC, followed by luminal A and luminal B, with HER2-enriched tumors showing the lowest rate of phospho-STAT3 immunostaining [ 58 ], suggesting that phospho-STAT3 may be a hallmark of more aggressive breast cancer subtypes. Other studies and meta-analyses have positively correlated nuclear phospho-STAT3 localization to highly differentiated tumors, higher tumor grade and lymphatic metastasis, though there appears to be no relationship to overall survival outcomes [ 59 , 60 ].…”

The interferon/STAT1 signaling axis is a common feature of tumor-initiating cells in breast cancer

“…STAT1 and STAT3, are expressed in many, but not all, human breast tumors (Wang et al, 2021; Widschwendter et al, 2002). At the mRNA level, 64.2% of breast tumors in the METABRIC cohort display comparatively elevated STAT3 mRNA levels (Aleskandarany et al, 2016).…”

“…At the mRNA level, 64.2% of breast tumors in the METABRIC cohort display comparatively elevated STAT3 mRNA levels (Aleskandarany et al, 2016). At the protein level, pSTAT3 is observed in ∼37.5% of TNBC patients, the highest of the three clinical subtypes (Wang et al, 2021). Although pSTAT1 has not been profiled as extensively in human breast tumors as pSTAT3, likely due to its known role as a tumor suppressor (Koromilas and Sexl, 2013), STAT1 activity has been detected using DNA binding assays and Western blot for pSTAT1 in a cohort of 73 breast cancer patients (Widschwendter et al, 2002).…”

Role of CTLA4 and pSTAT3 Immunostaining in Colorectal Carcinoma Prognosis and Treatment

“…Most of these studies revealed that pSTAT3 overexpression in many patients has a poor prognostic value. ( 36 , 37 ) Other studies found that pSTAT3 overexpression is related to better prognosis and favorable outcomes, particularly in thyroid and breast carcinoma ( 38 , 39 ).…”