title: Survivin expression in endometrial carcinoma: a tissue microarray study with correlation with PTEN and STAT-3.
abstract: Evasion of apoptotic cell death plays a key role in cancer development. Survivin is a member of the inhibitor of apoptosis proteins, which also has a role in the control of cell division. Survivin may be overexpressed in some tumors and has been suggested to be related to PTEN, beta-catenin, p53 [all of them frequently abnormal in endometrial carcinomas (ECs)], and STAT-3. A tissue microarray was constructed from paraffin-embedded blocks of 95 ECs, previously studied for microsatellite instability and for alterations in PTEN, k-RAS, and CTNNB-1. Immunohistochemical evaluation included 1) survivin, 2) markers of cell proliferation and apoptosis (Ki67-MIB1 and M 30-neoepitope cytokeratin 18), and 3) proteins involved in cell signaling pathways (PTEN, phospho-AKT, beta-catenin, p53, and STAT-3). Survivin expression was frequent in ECs (75.95%) but did not show any statistical significant correlation with histological type and grade, stage, overall survival, or mitotic and apoptotic indexes. Survivin expression had a statistical significant correlation with decreased PTEN expression (r = -0.383, p = 0.001), increased phospho-AKT (r = 0.70, p < 0.001), and positive STAT-3 immunostaining (r = 0.6, p < 0.001). Survivin expression did not show statistical correlation with either beta-catenin or p53 alterations. The results suggest that increased survivin expression is frequent in ECs and may be dependent on STAT-3 and PI3 K/AKT activation. Because PTEN abnormalities are very frequent in ECs, the results from this study indicate that PTEN may interfere with the process of apoptosis and cell proliferation by promoting survivin expression.
authors.affiliation: Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Pallares
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Martínez-Guitarte
authors.forename: Xavier
authors.initials: X
authors.lastname: Dolcet
authors.forename: David
authors.initials: D
authors.lastname: Llobet
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rue
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000077022:Survivin; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D051176:beta Catenin
chemical_list: C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human