Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the growth and invasion of several types of solid tumors. In this study, to assess the expression status and prognostic significance of the STAT3 pathway in upper urinary tract urothelial carcinoma (UTUC), we immunohistochemically stained for STAT3 and STAT3 pathway proteins, sphingosine-1-phosphate receptor 1 (S1PR1) and interleukin-6 (IL-6), in a tissue microarray containing 99 UTUC specimens. There were no significant associations between STAT3, S1PR1, or IL-6 expression pattern and tumor grade or pT stage. However, the patients with high STAT3 tumor had a significantly higher risk of both disease progression (p = 0.009) and cancer-specific mortality (p = 0.009), but not with tumors expressing S1PR1 or IL-6. High STAT3 expression in the nucleus was also associated with a significantly higher risk of both disease progression (p = 0.003) and cancer-specific mortality (p = 0.034). Multivariate analysis revealed that high STAT3 expression in the nucleus was significantly associated with cancer-specific survival after adjustment for pathological stage, lymph node involvement, lymphovascular invasion, and tumor grade (HR = 2.136, 95% CI = 1.009-4.767, p = 0.047). Our findings indicated that STAT3 could be a cancer-promoting factor and potentially a significant prognostic factor in UTUC.
PloS one. 2018 Aug 09*** epublish ***
Kyosuke Matsuzaki, Kazutoshi Fujita, Yujiro Hayashi, Makoto Matsushita, Satoshi Nojima, Kentaro Jingushi, Taigo Kato, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Ryoichi Imamura, Seiji Yamaguchi, Hiroaki Fushimi, Hiroshi Miyamoto, Eiichi Morii, Norio Nonomura
Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Department of Therapeutic Urologic Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Department of Urology, Osaka General Medical Center, Sumiyoshi-ku, Osaka, Japan., Department of Pathology, Osaka General Medical Center, Sumiyoshi-ku, Osaka, Japan., Departments of Pathology & Laboratory Medicine, Urology, and Oncology, University of Rochester Medical Center, Rochester, New York, United States of America.