The neural precursor cell expressed, developmentally down-regulated 4-like (Nedd4L) gene encodes an ubiquitin ligase that targets the epithelial sodium channel for degradation. Recent studies have demonstrated that Nedd4L plays a role in the progression of various cancers. However, the clinical implications of Nedd4L expression status in gastric cancer have remained unclear. We examined the Nedd4L expression in 82 gastric cancer patients by immunohistochemistry. The correlation between Nedd4L expression and clinicopathological factors, including prognosis, was evaluated. Cancerous Nedd4L expression was detectable in 36 of the 82 tumors (43.9%). Tumors with negative Nedd4L expression had greater extent of lymph node metastasis, lymphatic invasion, and venous invasion, and were at a worse stage than the tumors with positive Nedd4L expression. Additionally, the patients with negative Nedd4L expression had poor clinical outcomes. Furthermore, multivariate analysis indicated that Nedd4L expression was an independent prognostic factor for gastric cancer patients. Our results suggest for the first time that negative Nedd4L expression is strongly related to the invasion and metastasis of gastric cancer. Therefore, Nedd4L expression can be used as an independent prognostic marker of gastric cancer.

Objectivep21-activated kinase (PAK) 2, as a member of the PAK family kinases, is involved in a number of hallmark processes including cell proliferation, survival, mitosis, apoptosis, motility and angiogenesis. However, the clinical significance of the activation of PAK2 in human gastric cancer has not been fully elucidated. The aim of this study was to investigate whether PAK2 expression and its phosphorylation status are correlated with tumor progression and prognosis in gastric cancer.MethodsExpression patterns and subcellular localizations of PAK2 and Ser20-phosphorylated PAK2 (pSer20PAK2) in 82 gastric cancer patients were detected by immunohistochemistry.ResultsBoth PAK2 and pSer20PAK2 immunostainings were localized in the cytoplasm of tumor cells of gastric cancer tissues. Compared with the normal gastric mucosa, the expression levels of PAK2 and pSer20PAK2 proteins were both significantly increased (both P < 0.001). Additionally, the patients displaying the over-expression of PAK2 and pSer20PAK2 proteins were dramatically associated with unfavorable clinicopathologic variables including higher tumor depth (P = 0.022 and 0.036, respectively), greater extent of lymph node metastasis ((P = 0.022 and 0.036, respectively), positive distant metastasis (P = 0.025 and 0.038, respectively) and advanced tumor stage (P = 0.018 and 0.031, respectively). Moreover, the patients overexpressing PAK2 and pSer20PAK2 proteins have poor overall survival rates relative to those without overexpression of these proteins. Furthermore, cox multi-factor analysis showed that PAK2 (p = 0.012) and pSer20PAK2 (p = 0.010) were independent prognosis factors for human gastric cancer.ConclusionOur data suggest for the first time that PAK2 activation may be associated with advanced tumor progression and poor prognosis of gastric cancer.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1236344107120406.

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