title: Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging.
abstract: Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional surgical-pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. Two of the proteins identified, plectin and α-Actin-2, were used for validation studies using LC-MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI-MSI has the potential to identify discriminators of metastasis using primary tumour samples.
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Parul
authors.initials: P
authors.lastname: Mittal
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Manuela
authors.initials: M
authors.lastname: Klingler-Hoffmann
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Georgia
authors.initials: G
authors.lastname: Arentz
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Lyron
authors.initials: L
authors.lastname: Winderbaum
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Discipline of Obstetrics and Gynaecology, Research Centre for Reproductive Health, School of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Noor A
authors.initials: NA
authors.lastname: Lokman
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Lyndal
authors.initials: L
authors.lastname: Anderson
authors.affiliation: Faculty of Health and Medicine, University of New South Wales, Callaghan, New South Wales, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Scurry
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia, Austraila.
authors.forename: Yee
authors.initials: Y
authors.lastname: Leung
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia, Austraila.
authors.forename: Colin Jr
authors.initials: CJ
authors.lastname: Stewart
authors.affiliation: Department of Gynaecological Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carter
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Pulau Pinang, Malaysia.
authors.forename: Gurjeet
authors.initials: G
authors.lastname: Kaur
authors.affiliation: Discipline of Obstetrics and Gynaecology, Research Centre for Reproductive Health, School of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Austraila.|Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Austraila.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Oehler
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Austraila.|Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide, South Australia, Austraila.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffmann
mesh_terms: D003952:Diagnostic Imaging; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D010455:Peptides
keywords: Biomarker; Endometrial cancer; Lymph node metastasis; Proteomics