Abstract
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.
Highlights
Gastric cancer is one of the most common neoplasms in digestive system with highly malignant and a poor prognosis worldwide, especially in Asia and Africa [1]
Overexpression of PAK2 and pSer20PAK2 in human gastric cancer tissues Expression patterns and subcellular localizations of PAK2 and pSer20PAK2 in gastric cancer and normal gastric mucosa were detected by immunohistochemistry
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)
Summary
Gastric cancer is one of the most common neoplasms in digestive system with highly malignant and a poor prognosis worldwide, especially in Asia and Africa [1]. PAK2, which has an overall 76% homology with PAK1 and 96% homology in the kinase domain, has a dual role in both cell survival and cell death pathways. It is widely distributed throughout the body and is activated by binding with the small G protein complex Cdc42/Rac, but it is cleaved and activated by caspase-3 and similar proteases [9]. 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
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