Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy

Abstract

Background. The Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer. Methods. The expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classifi ed as negative or positive. We examined the expression of pAkt and its association with the clinicopathological fi ndings, prognosis, depth of invasion, the expression of p53, and effi cacy of oral fl uorouracil chemotherapy after surgery. Results. Expression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no signifi cant correlations between pAkt expression and the clinicopathological fi ndings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was signifi cant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fl uorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt-and p53-positive tumors showed a signifi cantly poorer prognosis than patients with either or both pAkt-and p53-negative tumors (P < 0.05). Conclusion. Our results indicate that pAkt expression may be useful for predicting the prognosis and effi cacy of fl uorouracil treatment in patients with gastric cancer.

Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer

“…Diverse opinions also exist regarding prognosis in relation to pAkt expressions. A large majority of studies have asserted that pAkt expression is correlated with poor prognosis in NSCLC [11,17,26], breast cancer [27], gastric cancer [20], and renal cell carcinoma [15]. However, Chan et al [28] have reported that pAkt expression is not significantly related to patient survival, but is inversely related to tumor grade and size in breast cancer.…”

“…Once activated, signaling through Akt can be propagated to a diverse array of substrates, including mTOR, a key regulator of protein translation [9]. Moreover, activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy [10][11][12][13][14] and is a poor prognostic factor for many cancers [15][16][17][18][19][20]. However, the prognostic significance and predictive value for response to therapy targeting activated Akt (phosphorylated Akt) or mTOR is not clearly established in the lung cancer patients.…”

Overexpression of eukaryotic elongation factor 1 alpha-2 is associated with poorer prognosis in patients with gastric cancer

“…Many previous studies from various countries have examined clinicopathologic prognostic factors for GC after radical gastrectomy. Researchers have regarded controversial factors, including sex, age at diagnosis, tumor diameter, gastric wall invasion, surgical margins, differentiation, lymph node metastasis, and TNM stage as independent prognostic factors in different reports (Murakami et al 2007;Shiraishi et al 2000;Yokota et al 2004;Zheng et al 2004). However, they did not reach a consensus concerning which clinicopathologic factors were associated with the optimum prognosis (Potrc et al 2007;Yokota et al 2002).…”

Overexpression of Phosphorylated Mammalian Target of Rapamycin Predicts Lymph Node Metastasis and Prognosis of Chinese Patients with Gastric Cancer

“…Among numerous proangiogenic factor, vascular endothelial growth factor (VEGF) has been established as the major angiogenic factor (17). Frequently observed in gastric cancer (18 -20), overexpression of VEGF closely correlates with lymph node metastasis (21), liver metastasis (22), age (23), and tumor size (24) and often indicates a poor prognosis (25,26) and therapy resistance (27). Although VEGF is constitutively expressed in many tumor cells, its expression is subject to several regulatory mechanisms (17).…”