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19-05-2010 | Oncology | Article

E17K substitution in AKT1 gene could indicate favorable prostate cancer course

Abstract

Free abstract

MedWire News: Dutch researchers have found a possible link between an amino acid mutation in the v-akt murine thymoma viral oncogene homolog 1 (AKT1) signaling pathway and a favorable clinical course in prostate cancer patients.

The three men with prostate cancer they have found so far with the somatic mutation lysine substitution for glutamate at position 17 (E17K) in AKT1 all had very long survival, despite also having aggressive clinicopathologic characteristics.

However, Joost Boormans (Erasmus University Medical Center, Rotterdam) and colleagues caution that “the findings of this study do not prove an association with better outcome because of the low prevalence of AKT1(E17K) in prostate cancer.”

The team has previously reported on the E17K substitution in AKT1 in a ductal prostate cancer patient who lived for more than 18 years with Gleason score 8 disease, and who did not die from it. Other studies have identified E17K in breast, ovarian, and colorectal cancer.

The current study sought the prevalence of AKT1(E17K) in a larger cohort of 214 patients, and investigated whether it was associated with a specific growth pattern or clinical outcome.

The researchers first examined 18 ductal prostate cancer samples for evidence of E17K substitution in AKT1 but found none. They concluded that: “An association between AKT1(E17K) and a specific ductal growth pattern of prostate cancer is unlikely.”

The team then analyzed 184 freshly frozen prostate tumor samples and found one patient harbored the AKT1(E17K) mutation. The patient had undergone radical prostatectomy for Gleason score 6 cancer with bladder neck involvement and positive surgical margins. However, despite these clinical characteristics, the patient was still alive after 17 years of follow-up.

To determine whether AKT1(E17K) is associated with favorable clinical outcome, the researchers analyzed 12 further prostate cancer patients with unfavorable clinicopathologic characteristics and survival longer than 13 years.

Again, one patient had the E17K substitution in AKT1, giving an overall prevalence of AKT1(E17K) of 1.4%.

“In a recent review, it was hypothesized that the presence of AKT1(E17K) is associated with a less aggressive form of cancer,” conclude Boormans et al in the British Journal of Cancer.

“The findings of our present series could be in agreement with such a hypothesis.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Sarah Guy

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