Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging

P. Mittal, M. Klingler-Hoffmann, G. Arentz, L. Winderbaum, N.A. Lokman, C. Zhang, L. Anderson, J. Scurry, Yee Leung, Colin Stewart, J. Carter, G. Kaur, M.K. Oehler, P. Hoffmann

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimMetastasis 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.
    Original languageEnglish
    Pages (from-to)1793-1801
    JournalProteomics
    Volume16
    Issue number11-12
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Endometrial Neoplasms
    Tumors
    Lymph Nodes
    Neoplasm Metastasis
    Imaging techniques
    Neoplasms
    Proteins
    Discriminators
    Ionization
    Mass spectrometry
    Desorption
    Plectin
    Lasers
    Validation Studies
    Actins
    Cause of Death
    Retrospective Studies
    Immunohistochemistry
    Peptides

    Cite this

    Mittal, P., Klingler-Hoffmann, M., Arentz, G., Winderbaum, L., Lokman, N. A., Zhang, C., ... Hoffmann, P. (2016). Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging. Proteomics, 16(11-12), 1793-1801. https://doi.org/10.1002/pmic.201500455
    Mittal, P. ; Klingler-Hoffmann, M. ; Arentz, G. ; Winderbaum, L. ; Lokman, N.A. ; Zhang, C. ; Anderson, L. ; Scurry, J. ; Leung, Yee ; Stewart, Colin ; Carter, J. ; Kaur, G. ; Oehler, M.K. ; Hoffmann, P. / Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging. In: Proteomics. 2016 ; Vol. 16, No. 11-12. pp. 1793-1801.
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    abstract = "{\circledC} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimMetastasis 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.",
    author = "P. Mittal and M. Klingler-Hoffmann and G. Arentz and L. Winderbaum and N.A. Lokman and C. Zhang and L. Anderson and J. Scurry and Yee Leung and Colin Stewart and J. Carter and G. Kaur and M.K. Oehler and P. Hoffmann",
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    Mittal, P, Klingler-Hoffmann, M, Arentz, G, Winderbaum, L, Lokman, NA, Zhang, C, Anderson, L, Scurry, J, Leung, Y, Stewart, C, Carter, J, Kaur, G, Oehler, MK & Hoffmann, P 2016, 'Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging' Proteomics, vol. 16, no. 11-12, pp. 1793-1801. https://doi.org/10.1002/pmic.201500455

    Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging. / Mittal, P.; Klingler-Hoffmann, M.; Arentz, G.; Winderbaum, L.; Lokman, N.A.; Zhang, C.; Anderson, L.; Scurry, J.; Leung, Yee; Stewart, Colin; Carter, J.; Kaur, G.; Oehler, M.K.; Hoffmann, P.

    In: Proteomics, Vol. 16, No. 11-12, 2016, p. 1793-1801.

    Research output: Contribution to journalArticle

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    AU - Mittal, P.

    AU - Klingler-Hoffmann, M.

    AU - Arentz, G.

    AU - Winderbaum, L.

    AU - Lokman, N.A.

    AU - Zhang, C.

    AU - Anderson, L.

    AU - Scurry, J.

    AU - Leung, Yee

    AU - Stewart, Colin

    AU - Carter, J.

    AU - Kaur, G.

    AU - Oehler, M.K.

    AU - Hoffmann, P.

    PY - 2016

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    N2 - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimMetastasis 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.

    AB - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimMetastasis 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.

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    M3 - Article

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    JF - Proteomics

    SN - 1615-9853

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    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C et al. Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging. Proteomics. 2016;16(11-12):1793-1801. https://doi.org/10.1002/pmic.201500455