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17-04-2012 | Surgery | Article

RNA-binding protein influences bladder cancer prognosis

Abstract

Free abstract

MedWire News: High protein expression of insulin-like growth factor messenger RNA (mRNA)-binding protein 3 (IMP3) may predict poor patient survival in muscle-invasive bladder cancer, report researchers.

"Integration of IMP3 expression status in the everyday decision-making mechanisms may help to improve therapy," they say.

Only 50% of patients undergoing radical cystectomy for muscle-invasive bladder cancer will have a long disease-free survival, while the other 50% of patients will suffer from cancer progression and ultimately die, explain Tibor Szarvas (Medical University of Vienna, Austria) and colleagues.

Previous research has shown the prognostic relevance of IMP3 expression in a series of cancers but its relevance has not yet been assessed in muscle-invasive bladder cancer, say the researchers. In addition, little information is available about the molecular actions of IMP3.

Two molecular targets for IMP3 - insulin growth factor 2 (IGF2) and CD44 - have been identified, write Szarvas et al, but they have not yet been confirmed in tumor samples and the relevance of these IMP3 targets in cancer formation and progression is therefore unknown.

Using realtime polymerase chain reaction (RT-PCR) and immunohistochemical (IHC) analyses, Szarvas and team analyzed IMP3 protein and gene expression in tumor samples from 224 patients who underwent surgical treatment for bladder cancer at the University Hospital of Essen, Germany, between 1990 and 2004. They also investigated the expression of CD44, IGF2, and the IGF2 receptor, IGF1-R.

Patients with frozen tissue samples available (RT-PCR group; n=118) were followed up for a median of 20 months and those with paraffin-embedded tissue sections available (IHC cohort; n=106) were followed up for a median of 15 months.

As reported in BJU International, the researchers found that levels of IMP3 protein and gene expression were significantly enhanced in high-stage (T2-4), high-grade (G3) bladder cancers, compared with low-stage (Ta-1), low-grade (G1-2) cancers.

Multivariate analysis revealed that high IMP3 tissue expression (histochemical score >8) but not high gene expression (relative expression >0.0135) was a significant predictor for the disease-specific survival and overall survival of patients with muscle-invasive bladder cancer, at hazard ratios of 2.58 and 2.07, respectively.

By contrast, IGF2, IGF1-R, and CD44 expression did not show any impact on patients' prognosis.

"The tumor promoting effect of IMP3 is independent of its regulatory action on IGF2 and CD44 expression," say the researchers. "Therefore, further research is needed to elucidate its exact role in tumour progression."

The team concludes that high IMP3 protein levels may identify patients at high risk for bladder cancer progression and may therefore select patients for a more intensive therapy or for a strict follow up.

Furthermore, based on its high expression level in high-grade bladder tumors and its clear association with disease-free progression, IMP3 may serve as a target for cancer therapy.

By Sally Robertson

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