Stress-Inducible Gene May Promote Aggressive Bladder Cancer
Key findings
- There is growing evidence that immediate early response gene 3 (IER3) can promote tumor development and regulate tumor growth
- In the first study in bladder cancer, Massachusetts General Hospital researchers observed overexpression of IER3 protein in the cytoplasm of human bladder cancer cells
- High IER3 expression was associated with aggressive progression of bladder cancer and predicted poor overall survival
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Immediate early response gene 3 (IER3), a stress-inducible gene, seems to play a complex and contradictory role in cell cycle control and apoptosis. There is evidence for its being either an oncogene or, in contrast, a tumor suppressor gene. However, an increasing number of studies suggest that IER3 promotes tumor development such as in pancreatic cancer, lung cancer and Hodgkin's lymphoma, and regulates tumor growth.
Researchers at Massachusetts General Hospital recently participated in the first study of IER3 in bladder cancer and report in BMC Urology that it appears to be a prognostic marker.
Chin-Lee Wu, MD, PhD, associate pathologist and director of Genitourinary Pathology Services, and team examined 88 bladder cancer tissue samples obtained from patients treated at Mass General between 2002 and 2010. The researchers performed immunohistochemistry analysis to examine the subcellular localization and the expression levels of IER3 protein.
The researchers evaluated the gene's expression in each tissue section according to the immunostaining intensity and percentage. They multiplied the intensity of immunostaining (scale of 0–3) by the percentage of immunostaining (scale of 0–4) to obtain an immunoreactivity score (scale of 0–12).
They found that IER3 was mainly localized in the cytoplasm of bladder cancer cells. Based on the immunoreactivity score, they dichotomized IER3 expression as low (immunoreactivity score of 0–3, 57.7% of patients) or high (4–12, 44.3% of patients).
Patients with high IER3 expression were significantly more likely than those with low expression to have a high pathologic nodal stage (=.018). No other clinicopathologic feature studied was associated with IER3 expression, including age, gender, pathological stage, perineural invasion, lymphovascular invasion, soft tissue surgical margins or distant metastasis.
Kaplan-Meier analysis showed that patients with high IER3 expression had worse overall survival than those in the low expression group (=.002). On multivariate survival analysis, IER3 protein expression was an independent prognostic indicator, as important as age and pathologic nodal stage.
Dr. Wu's group calls for research into the molecular mechanisms that underlie IER3 involvement in bladder cancer.
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