Phosphorylation of signal transducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis

Abstract

Signal transducer and activator of transcription (STAT) 3 mediates a broad range of biological processes, including cell survival and proliferation, and STAT3 has generally been regarded as a pro-oncogenic transcription factor. We investigated the phosphorylation status of STAT3 and the protein expression of the suppressor of cytokine signaling 3 (SOCS3) by immunohistochemistry in 145 formalin-fixed, paraffin-embedded samples of soft tissue leiomyosarcoma (LMS), including 129 primary tumors. Eight benign soft tissue smooth muscle tumors were also examined. Thirteen frozen LMS samples, which were paired with normal tissue samples, were assessed by Western blot analysis for the phosphorylation of STAT3 and SOCS3 expression. Immunohistochemical study showed that the phosphorylation of STAT3 was not a major event in LMS (37%). Moreover, phosphorylated STAT3 (pSTAT3) expression was significantly correlated with a better prognosis. Overexpression of SOCS3 was recognized in 52% of the cases and negatively correlated with pSTAT3 expression. Among the benign tumors, 63 and 25% were positive for pSTAT3 and SOCS3, respectively. Immunoblotting detected pSTAT3 in all tumor samples, but at lower levels than in non-neoplastic tissue. SOCS3 was detected in 92% (12 out of 13) of tumor tissues, but in none of the normal tissues. Contrary to the previous investigations of many other malignant tumors, STAT3 was inactivated in most LMS cases, likely owing to SOCS3 overexpression. STAT3 might not contribute to the progression of soft tissue LMS, and the phosphorylation status of STAT3 has the potential to be a favorable prognostic marker of LMS.

The Role of STAT3 in Thyroid Cancer

“…Intriguingly, it has also been reported that high nuclear expression of Tyr705-phosphorylated STAT3 is correlated with improved survival, smaller tumors, or less aggressive histology in various tumors, including breast cancer [73,74], head and neck cancer [75], lung cancer [76], gastric cancer [77], soft tissue leiomyosarcoma [78], and advanced rectal cancer [79]. However, in pancreatic ductal adenocarcinoma, no association was seen between STAT3 phosphorylation and patient survival [80].…”

The prognostic values of signal transducers activators of transcription family in ovarian cancer

“…Grabner et al [33] detected STAT3 may act as a tumor suppressor through STAT3-NF-κB-IL-8 axis in KRAS mutant lung adenocarcinoma and a molecular marker with favorable prognostic value. In the same line of evidence, it was shown that p-STAT3 was reported as a favorable prognosis marker in breast cancer [15], head and neck squamous cell carcinoma [16], and leiomyosarcoma [34]. Amongst the STAT family, STAT3 is the most studied STAT in ovarian cancer.…”

Phosphorylation of STAT3 in Undifferentiated Pleomorphic Sarcoma Is Correlated with a Favorable Prognosis

“…Suppression of SOCS3 causes the development of cancer cells in the human lung [24] . On the other hand, SOCS3 overexpression suppresses the apoptosis pathway in prostate cancer and is associated with decreased survival in leiomyosarcoma [5,25] . The function of SOCS3 in neoplasms thus remains controversial.…”

“…STAT proteins are then phosphorylated, and they translocate to the nucleus and exert transcriptional control. Although sev-eral studies have linked STAT3 to tumor growth and metastases in various types of neoplasms [3,4] , it was reported that STAT3 activation is also correlated with a better prognosis in some tumors [5,6] . STAT3 seems to have a double-sided effect on tumor progression.…”

“…p-STAT3 immunoreactivity was judged as positive when the proportion of tumor cells that stained more strongly than adjacent endothelial cells was ≥ 10% [5] . SOCS3 immunopositivity was scored from 0 to 4 for the percentage of positive cells and from 0 to 3 for staining intensity with reference to a previous report [18] .…”