Immunohistochemical expression of phospho-mTOR is associated with poor prognosis in patients with gallbladder
Pamela Leal1, Patricia García, Alejandra Sandoval
1Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile.
Context:
Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear.
Objective:
To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma.
Design:
Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis.
Results:
Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02).
Conclusions:
Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.
Insights
High phospho-mammalian target of rapamycin (mTOR) expression is linked to poorer outcomes in advanced gallbladder carcinoma (GBC). This suggests mTOR activation is an early event in GBC development and a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Advanced gallbladder carcinoma (GBC) presents a significant clinical challenge due to its high fatality rate and limited treatment options.
- The mammalian target of rapamycin (mTOR) pathway is crucial for cell growth and homeostasis, with dysregulation observed in various cancers, making it a promising therapeutic target.
- The role and expression status of mTOR in GBC remain largely uncharacterized.
Purpose of the Study:
- To investigate the immunohistochemical expression of phospho-mTOR in advanced GBC.
- To determine the prognostic significance of phospho-mTOR expression in advanced GBC patients.
- To explore the association between phospho-mTOR expression and clinicopathological features.
Main Methods:
- Immunohistochemistry was employed to assess phospho-mTOR expression in 128 advanced GBC tissue samples and 99 chronic cholecystitis cases.
- Cases were categorized based on the presence or absence of metaplasia and further classified into low or high phospho-mTOR expression groups.
- Statistical analyses, including Kaplan-Meier survival curves, were utilized to evaluate correlations between phospho-mTOR levels, clinical variables, and patient survival.
Main Results:
- Phospho-mTOR expression was detected in 64.1% of advanced GBCs, significantly higher than in chronic cholecystitis cases (24%).
- High phospho-mTOR expression was significantly associated with a poorer prognosis in patients with advanced GBC (P = .02).
- Metaplasia, a precursor lesion, was common in chronic cholecystitis, and mTOR activation appears to occur early in GBC development.
Conclusions:
- mTOR pathway activation is an early event in gallbladder carcinoma development, potentially contributing to carcinogenesis.
- Elevated phospho-mTOR expression serves as a significant prognostic biomarker for poor survival in advanced GBC.
- These findings underscore the potential of targeting the mTOR pathway for novel therapeutic strategies in GBC.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...