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Article

MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia

by
Chao Zhang
1,2,†,
Georgia Arentz
1,2,†,
Lyron Winderbaum
1,†,
Noor A. Lokman
1,3,
Manuela Klingler-Hoffmann
1,2,
Parul Mittal
1,2,
Christopher Carter
4,
Martin K. Oehler
3,5 and
Peter Hoffmann
1,2,*
1
Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide 5005, Australia
2
Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide 5005, Australia
3
Discipline of Obstetrics and Gynaecology, School of Medicine, Research Centre for Reproductive Health, Robinson Institute, Adelaide 5005, Australia
4
Department of Cytopathology, SA Pathology, Adelaide 5005, Australia
5
Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide 5005, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2016, 17(7), 1088; https://doi.org/10.3390/ijms17071088
Submission received: 10 May 2016 / Revised: 24 June 2016 / Accepted: 30 June 2016 / Published: 8 July 2016
(This article belongs to the Special Issue Cancer Molecular Imaging in the Era of Precision Medicine)

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.
Keywords: Matrix-assisted laser desorption/ionization (MALDI); imaging mass spectrometry (MSI); differentiated vulvar intraepithelial neoplasia (dVIN); vulva squamous cell carcinomas (VSCC); Cytokeratin 5 (CK5) Matrix-assisted laser desorption/ionization (MALDI); imaging mass spectrometry (MSI); differentiated vulvar intraepithelial neoplasia (dVIN); vulva squamous cell carcinomas (VSCC); Cytokeratin 5 (CK5)
Graphical Abstract

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MDPI and ACS Style

Zhang, C.; Arentz, G.; Winderbaum, L.; Lokman, N.A.; Klingler-Hoffmann, M.; Mittal, P.; Carter, C.; Oehler, M.K.; Hoffmann, P. MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia. Int. J. Mol. Sci. 2016, 17, 1088. https://doi.org/10.3390/ijms17071088

AMA Style

Zhang C, Arentz G, Winderbaum L, Lokman NA, Klingler-Hoffmann M, Mittal P, Carter C, Oehler MK, Hoffmann P. MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia. International Journal of Molecular Sciences. 2016; 17(7):1088. https://doi.org/10.3390/ijms17071088

Chicago/Turabian Style

Zhang, Chao, Georgia Arentz, Lyron Winderbaum, Noor A. Lokman, Manuela Klingler-Hoffmann, Parul Mittal, Christopher Carter, Martin K. Oehler, and Peter Hoffmann. 2016. "MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia" International Journal of Molecular Sciences 17, no. 7: 1088. https://doi.org/10.3390/ijms17071088

APA Style

Zhang, C., Arentz, G., Winderbaum, L., Lokman, N. A., Klingler-Hoffmann, M., Mittal, P., Carter, C., Oehler, M. K., & Hoffmann, P. (2016). MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia. International Journal of Molecular Sciences, 17(7), 1088. https://doi.org/10.3390/ijms17071088

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