Original Article Activation of Stat3 in renal tumors
Charles Guo, Peng Lee, Guanyu Yang, Kyle Khun, Xiantian Kong, David Levy, Jonathan Melamed
Department of Pathology, New York University School of Medicine, New York, NY
Received February 17, 2009; accepted February 25, 2009; available online February 28, 2009
Abstract: Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target. (AJTR902003).
Key words: Signal transducer and activator of transcription 3 (Stat3), renal tumor, kidney cancer
Address all correspondence to: Peng Lee, MD, PhD Department of Pathology New York University School of Medicine New York, NY 10016, Tel: (212)951-3418 E-mail: peng.lee@nyumc.org;
Jonathan Melamed, MD Department of Pathology New York University School of Medicine 550 First Avenue, Room TH459 New York, NY 10016, Tel: (212)263-8927 E-mail: jonathan.melamed@nyumc.org