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Mammalian target of rapamycin is a biomarker of poor survival in metastatic serous ovarian carcinoma
- Source :
- Human Pathology. 41:794-804
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- The AKT signaling pathway is crucial for cancer cell survival. The objective of this study was to analyze the expression and clinical role of this pathway in serous ovarian carcinoma. Phospho-AKT and phospho-mammalian target of rapamycin protein expression was studied in 269 ovarian carcinomas (159 effusions, 38 primary carcinomas, 72 solid metastases) using immunohistochemistry. The association between AKT, mammalian target of rapamycin, and DJ-1 in effusions was quantitatively analyzed using flow cytometry. AKT phosphorylation status in effusions was further studied using Western blotting. Phospho-AKT and phospho-mammalian target of rapamycin were detected in the majority of tumors at all anatomical sites. Phospho-AKT expression in effusions was higher in grade 3 versus grades 1 and 2 tumors (P = .013). Flow cytometry analysis showed association between AKT, mammalian target of rapamycin, and DJ-1 expression (P < .001). Higher phospho-AKT Thr308/pan-AKT ratio by Western blotting was associated with more advanced International Federation of Gynecology and Obstetrics stage (P = .018) and a trend for poor response to chemotherapy at first disease recurrence (P = .051). Higher phospho-mammalian target of rapamycin protein expression in effusions by immunohistochemistry was associated with poor progression-free survival for patients with postchemotherapy effusions (P = .005). Phospho-mammalian target of rapamycin was an independent predictor of poor progression-free survival for patients with postchemotherapy effusions (P = .03). The association between activated AKT and mammalian target of rapamycin expression and clinicopathologic parameters of aggressive disease, including shorter patient survival, provides further evidence regarding the central role of this signaling pathway in ovarian carcinoma.
- Subjects :
- Adult
Oncology
medicine.medical_specialty
Protein Deglycase DJ-1
Protein Serine-Threonine Kinases
Biology
Pathology and Forensic Medicine
Ovarian carcinoma
Internal medicine
Biomarkers, Tumor
medicine
Ascitic Fluid
Humans
Phosphorylation
Survival rate
Protein kinase B
Peritoneal Neoplasms
PI3K/AKT/mTOR pathway
Aged
Neoplasm Staging
Aged, 80 and over
Oncogene Proteins
Ovarian Neoplasms
Akt/PKB signaling pathway
TOR Serine-Threonine Kinases
Cystadenoma, Serous
Intracellular Signaling Peptides and Proteins
Middle Aged
Phosphoproteins
Prognosis
Pleural Effusion, Malignant
Survival Rate
Serous fluid
Immunohistochemistry
Female
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 00468177
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Human Pathology
- Accession number :
- edsair.doi.dedup.....6924ab2a26cb52f9ef60c73f04926b3e