title: MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia.
abstract: Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC.
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. chao.zhang01@student.adelaide.edu.au.|Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia. chao.zhang01@student.adelaide.edu.au.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. georgia.arentz@adelaide.edu.au.|Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia. georgia.arentz@adelaide.edu.au.
authors.forename: Georgia
authors.initials: G
authors.lastname: Arentz
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. lyron.winderbaum@student.adelaide.edu.au.
authors.forename: Lyron
authors.initials: L
authors.lastname: Winderbaum
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. noor.lokman@adelaide.edu.au.|Discipline of Obstetrics and Gynaecology, School of Medicine, Research Centre for Reproductive Health, Robinson Institute, Adelaide 5005, Australia. noor.lokman@adelaide.edu.au.
authors.forename: Noor A
authors.initials: NA
authors.lastname: Lokman
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. manuela.klinglerhoffmann@adelaide.edu.au.|Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia. manuela.klinglerhoffmann@adelaide.edu.au.
authors.forename: Manuela
authors.initials: M
authors.lastname: Klingler-Hoffmann
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. parul.mittal@adelaide.edu.au.|Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia. parul.mittal@adelaide.edu.au.
authors.forename: Parul
authors.initials: P
authors.lastname: Mittal
authors.affiliation: Department of Cytopathology, SA Pathology, Adelaide 5005, Australia. Christopher.Carter@sa.gov.au.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carter
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Research Centre for Reproductive Health, Robinson Institute, Adelaide 5005, Australia. martin.oehler@adelaide.edu.au.|Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide 5005, Australia. martin.oehler@adelaide.edu.au.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Oehler
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia. Peter.hoffmann@adelaide.edu.au.|Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia. Peter.hoffmann@adelaide.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D053555:Keratin-5; D010455:Peptides
keywords: Cytokeratin 5 (CK5); Matrix-assisted laser desorption/ionization (MALDI); differentiated vulvar intraepithelial neoplasia (dVIN); imaging mass spectrometry (MSI); vulva squamous cell carcinomas (VSCC)