title: Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer.
abstract: The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
authors: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, SA 5005; Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, SA 5005.
authors: Parul
authors: P
authors: Mittal
authors: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, SA 5005; Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, SA 5005.
authors: Manuela
authors: M
authors: Klingler-Hoffmann
authors: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, SA 5005; Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, SA 5005.
authors: Georgia
authors: G
authors: Arentz
authors: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, SA 5005; Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, SA 5005.
authors: Lyron
authors: L
authors: Winderbaum
authors: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors: Gurjeet
authors: G
authors: Kaur
authors: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors: Lyndal
authors: L
authors: Anderson
authors: Faculty of Health and Medicine, University of New South Wales, Callaghan, New South Wales, Australia.
authors: James
authors: J
authors: Scurry
authors: School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia, Australia.
authors: Yee
authors: Y
authors: Leung
authors: School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia, Australia.
authors: Colin Jr
authors: CJ
authors: Stewart
authors: Department of Gynaecological Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
authors: Jonathan
authors: J
authors: Carter
authors: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, SA 5005; Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, SA 5005. Electronic address: peter.hoffmann@adelaide.edu.au.
authors: Peter
authors: P
authors: Hoffmann
authors: Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, Robinson Institute, The University of Adelaide, SA 5005; Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA 5005, Australia. Electronic address: martin.oehler@adelaide.edu.au.
authors: Martin K
authors: MK
authors: Oehler
mesh_terms: D000185:Actinin / Q000378:metabolism*; D017306:Annexin A2 / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D015536:Down-Regulation / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D015854:Up-Regulation / Q000502:physiology
chemical_list: D017306:Annexin A2; D000185:Actinin
keywords: Annexin A2; Endometrial cancer; Label free LC-MS/MS; MALDI MSI; Metastasis; α actinin 4