Activated Akt expression is associated with the recurrence of primary melanomas and further refines the prognostic and predictive values for relapse in acral melanomas
Kohei Nojima, Masahiro Hayashi, Atsushi Tanemura, Hind Al‐Busani, Toru Saito, Tamio Suzuki, Masashi Ishikawa, Taisuke Mori, Shogo Wada, Naoya Yamazaki, Ichiro Katayama, Hiroki Mori, Hiroo Yokozeki, Naoko Okiyama, Yoshiyuki Sasaki, Takeshi Namiki- Dermatology
- General Biochemistry, Genetics and Molecular Biology
- Oncology
Abstract
A PTEN deficiency leads to the activation of phospho‐Akt at serine 473 (p‐Akt) and promotes the tumorigenesis of melanomas by coupling with NUAK2 amplification. We tested the prognostic impact of p‐Akt and/or NUAK2 expression on the relapse‐free survival (RFS) and overall survival (OS) of melanoma patients. Primary tumors from patients with acral melanomas (112), Low‐cumulative sun damage (CSD) melanomas (38), and High‐CSD melanomas (18) were examined using immunohistochemistry and their prognostic significance was analyzed statistically. The expression of p‐Akt was found in 32.1%, 68.4%, and 55.6% of acral, Low‐CSD, and High‐CSD melanomas, while NUAK2 expression was found in 46.4%, 76.3%, and 50.0%, respectively. Either p‐Akt or NUAK2 expression was inversely correlated with the RFS of primary melanoma patients and acral melanoma patients (p‐Akt: p < .0001, p < .0001; NUAK2; p = .0005, p < .0001, respectively). Strikingly, multivariate analyses revealed that p‐Akt had a significant impact on RFS (Hazard ratio = 4.454; p < .0001), while NUAK2 did not. Further subset analyses revealed that p‐Akt expression had an inferior RFS of patients with acral melanomas (Hazard ratio = 4.036; p = .0005). We conclude that the expression of p‐Akt has a significant impact on RFS of patients with primary melanomas and can predict the relapse of patients with acral melanomas.