Phosphorylation of signal transducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis.
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.
Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Nokitaka
N
Setsu
Kenichi
K
Kohashi
Makoto
M
Endo
Hidetaka
H
Yamamoto
Sadafumi
S
Tamiya
Yusuke
Y
Takahashi
Yuichi
Y
Yamada
Takeaki
T
Ishii
Shuichi
S
Matsuda
Ryohei
R
Yokoyama
Yukihide
Y
Iwamoto
Yoshinao
Y
Oda
D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011379:Prognosis; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
D050828:Protein Inhibitors of Activated STAT; 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; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6