A new prognostic biomarker for breast cancer

A new method of molecular imaging captures the dysfunction of an oncoprotein—Akt/PKB, the activation of which is tied to dismal prognoses in cancer patients. High throughput time-resolved-FRET (fluorescence resonance energy transfer) was implemented to seek out Akt/PKB activation in breast cancer patients, which could have a significant impact on not only future research, but potentially individual patient management, according to a study published in the July issue of Cancer Research.

Selvaraju Veeriah, a research fellow from Cell Biophysics and Protein Phosphorylation Laboratory, Cancer Research UK in London, and colleagues developed a technique for revealing the disregulation of Akt/PKB, involved in new vascularization, glucose metabolism, cellular proliferation and stability of the genome. Akt activation marks a poor prognosis and resistance to treatment with radiotherapy.

“Dysregulation of the Akt/PKB pathway has been associated with poor prognosis in several human carcinomas,” wrote Veeriah et al. “Current approaches to assess Akt activation rely on intensity-based methods, which are limited by the subjectivity of manual scoring and poor specificity. Here we report the development of a novel assay using amplified, time resolved-FRET, which is highly specific and sensitive and can be adapted to any protein.”

The researchers worked with 230 cores of ER positive and negative breast tissue from a tumor bank at Guys Hospital in London and evaluated the binding specificity of human anti-Akt antibodies panAkt and pT308. Immunofluorescence labeling and FRET assays were performed followed by a comprehensive statistical analysis. Results of the research showed that the histology grade was the most important independent factor for disease free and overall survival.

“These findings show that FRET efficiency, as an indicator of Akt activation status, but not intensity ratio, predicts poorer disease-free and overall survival in patients with ER positive primary breast carcinoma,” the researchers concluded.