Expression of PI3K-AKT-mTOR signaling pathway in gastric cancer

Abstract

Background: The PI3K/AKT/m TOR pathway is activated in gastric cancer (GC). This pathway may be an appropriate target for GC therapy. Such therapy may involve inhibiting cell proliferation, enhancing apoptosis, and restoring the sensitivity of cancer cells to chemotherapy. Aim: To study the expression of the PI3K/AKT/mTOR pathway in Egyptian patients with GC. Methods: Enrolled Patients were divided into 2 groups, group 1 included 23 patients with lymph node metastatic (LNM) gastric cancer (GC) and group 2 included 10 patients with non-metastatic GC. Liver and renal biochemical tests, CBC, H. pylori testing, CEA, CA19-9 & metastatic radiological work up were done. Upper Gastrointestinal endoscopy was done to diagnose the site, size and morphology of GC and to take biopsy from the suspicious lesion, adjacent mucosa and all parts of the stomach. Enrolled patients had received surgical resection when appropriate. The harvested tumor tissue was processed for histopathology as well as Immunohistochemical staining (IHC) for detection of expression of PI3K/AKT/mTOR. IHC score for the expression of mTOR, AKT & PI3K (ranging from 0 to 12) was calculated as follows: Grade of stain intensity × Grade of coloration rate. A score ≥4 was considered positive. Results: The mTOR expression was positive in 54.5%, AKT expression was positive in 72.7% & PI3K expression was positive in 36.4% of cases. There was significantly higher expression of AKT in metastatic (87%) than non-metastatic GC (40%), p=0.010. AKT expression was significantly higher in LNM GC (median score was 12) than non-metastatic GC (median score was 2.5), p=0.028. AKT score at cutoff value of more than 3 was a statistically significant discriminator between LNM and non-metastatic GC, AUC=0.743, p=.014, sensitivity, 87% & specificity, 60%. Conclusion: The mTOR expression was positive in 54.5%, AKT expression was positive in 72.7% & PI3K expression was positive in 36.4% of GC cases. AKT expression score may discriminate between LN metastatic and non-metastatic gastric cancer