Overview of MDM2 and B-RAF Expression in Gastric Lesions

Abstract

BACKGROUND:Globally, gastric cancer (GC) it is the fourth most common cancer and the third cause of cancer-related deaths. Overexpression of MDM2 and B-RAF appeared to be increased in malignancy and associated with poor prognosis in several human tumours, but their role in gastric cancer remains controversial.AIM:We had investigated the immunohistochemical expression of MDM2 and B-RAF in 136 gastric lesions with/without H. pylori association.MATERIAL AND METHODS:Studied specimens include chronic gastritis (32), intestinal type GC (70), diffuse GC (22) and gastrointestinal stromal tumours (GIST) (12).RESULTS:MDM2 expression increased significantly in intestinal GC compared to other groups (p < 0.001), while B-RAF expression increased significantly in GIST compared to other groups (p < 0.001). H. pylori increased expression of MDM2 in intestinal GC cases but did not affect B-RAF expression. MDM2 expression correlated with high grade of tumor differentiation (p < 0.001), deep invasion (p < 0.05), nodal metastases (p < 0.05) and distant metastases (p < 0.1) in intestinal GC, while B-RAF expression did not correlate with TNM stage (p < 0.1).CONCLUSION:MDM2 up-regulation was more frequent in intestinal GC, while B-RAF up-regulation was more frequent in GIST compared to other groups; MDM2 expression in intestinal GC was correlated with H. pylori association, high grade of differentiation, deep invasion, nodal and distant metastases, meanwhile, B-RAF expression was correlated with high-grade intestinal GC but did not correlate with H. pylori or TNM stage. The possible role of both MDM2 and B-RAF in predicting progression of gastric tumours and prognosis deserves further investigations.

Hyperactivation of MEK/ERK pathway by Ca2+/calmodulin‐dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin‐dependent kinases and minichromosome maintenance protein in gastric cancer cells

“…MAPK signaling pathway is reported to be involved in GC invasion and metastasis 35 BRAF, a member of RAF/MEK/ERK signaling pathway, is usually activated by a complex series of events 36 . BRAF is the most frequently mutated serine/threonine kinase in human cancers, 37 it is mutated in approximately 7% of all cancers, including GC, 38,39 and its overexpression is reported in GC 40 . RAF family members can phosphorylate and activate MEK and ERK with different biochemical potencies 41,42 .…”

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

“…Being a P53-specific E3 ubiquitin ligase, MDM2 is a principal factor in P53 destruction (28). MDM2 has proved to play an essential role in cancer progression by inducing cell proliferation, invasion, and therapeutic resistance and inhibiting the apoptotic process, serving as a useful predictive marker for poor prognosis in various human cancers such as GC, breast cancer, hepatocellular carcinoma, and lung cancer (11,(29)(30)(31). MDM2 expression parameters are closely correlated with H. pylori infection and higher stages GC (29).…”

Association of Murine Double Minute 2 polymorphisms with gastric cancer: A systematic review with meta‑analysis

“…Studies have shown that MDM2 amplification has been detected in several types of cancer, including GC (10,19). In GC, MDM2 has been shown to be amplified (12) and overexpressed in GC tissues (36,37), and this has also been associated with a higher grade of tumor differentiation, deeper invasion and nodal and distant metastasis (37).…”