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Activation of Stat3 in renal tumors
Charles Guo1, Guanyu Yang, Kyle Khun
1Department of Pathology, New York University School of Medicine New York, NY.
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.
Insights
Activated Signal transducer and activator of transcription 3 (Stat3) is more prevalent in aggressive kidney cancers. This finding suggests Stat3 activation could be a prognostic marker or therapeutic target for renal cell carcinoma (RCC).
Area of Science:
- Molecular Biology
- Oncology
- Signal Transduction
Background:
- Signal transducer and activator of transcription 3 (Stat3) is crucial in cell transformation and apoptosis inhibition.
- Persistent Stat3 activation is observed in various human cancers.
- Previous research indicates Stat3 activation in renal cell carcinoma (RCC), but detailed patterns across histologic types are unknown.
Purpose of the Study:
- To characterize the expression pattern of activated Signal transducer and activator of transcription 3 (pStat3) in different histologic types of renal tumors.
- To investigate the correlation between Stat3 activation and tumor malignancy potential.
- To explore the potential of Stat3 activation as a prognostic marker or therapeutic target in renal neoplasia.
Main Methods:
- Immunohistochemical analysis of phosphorylated Stat3 (pStat3) using a specific anti-pStat3 antibody.
- Utilized a tissue microarray comprising various renal tumor types: conventional clear cell RCC, chromophobe RCC, papillary RCC, oncocytoma, urothelial carcinoma, and normal kidney tissue.
- Quantified nuclear pStat3 staining to assess Stat3 activation levels.
Main Results:
- Positive nuclear pStat3 staining was detected in 59.5% of conventional clear cell RCC, 33.3% of chromophobe RCC, and 57.1% of papillary RCC.
- Urothelial carcinomas showed high pStat3 positivity (85.7%), while oncocytomas had lower positivity (26.7%).
- Non-neoplastic kidney tissue exhibited weak pStat3 immunoreactivity in 19.0% of cases, with increased Stat3 activation correlating with higher malignant potential in renal tumors.
Conclusions:
- Stat3 activation is elevated in renal tumors with greater malignant potential, including conventional clear cell RCC, papillary RCC, and urothelial carcinoma.
- Chromophobe RCC shows a slight increase, whereas oncocytoma does not exhibit increased Stat3 activation.
- These findings highlight the role of Stat3 activation in renal neoplasia and suggest its potential as a prognostic biomarker or therapeutic target.
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