Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer

Abstract

BackgroundPTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC.MethodsThe immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor.ResultsThe group was comprised of 108 patients, 91 women (84.3 %) and 17 men (15.7 %) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33 %) were early carcinomas (EC) and the remaining 73 (67 %) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3 %). Only in three AC (4.1 %) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53 % at 10 months.DiscussionLoss of PTEN expression was observed in 4.1 % of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.

Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway

“…PTEN is downregulated by glycine in microglia. PTEN is a tumor suppressor, and the inhibition of PTEN activates AKT through the PI3K signaling pathway (46,47). The downregulation of PTEN has a neuroprotective effect on ischemic stroke injury.…”

“…PTEN is a tumor suppressor, and the inhibition of PTEN activates AKT through the PI3K signaling pathway (46,47). The inhibition of PTEN reduces ischemia-induced neuronal death (48).…”

Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer

“…We generate ortho-and heterotopic GBCs featuring the most frequent genetic alterations (p53 together with mutant KRAS, as well as p53 in conjunction with mutant ERBB2). Tumors develop with 100% penetrance and can be generated with and without loss of Pten, a gene that is inactivated in a subset of human GBCs [18,31]. Since murine Erbb2 is known to be less oncogenic than its human counterpart, we introduced the human ERBB2 gene [32].…”

Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

“…Aberrations in the PI3K/AKT/ mTOR pathway, such as PI3K mutations, PI3KCA amplifications, phosphorylated AKT (p-AKT), and p-mTOR overexpression, have been detected in BTCs and are associated with poorer prognosis [74]. The loss of expression of PTEN, a tumour suppressor gene involved in the regulation of the PI3K/AKT/mTOR pathway, has also been found in 4.1-51.8% of GBC [75,76]. Thus far, early-phase clinical studies of an AKT inhibitor (MK-2206) [77], an mTOR inhibitor (everolimus) [78], and a PI3K inhibitor (buparlisib) together with FOLFOX [79] have shown limited tumour responses.…”