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HMGA2 protein expression in ovarian serous carcinoma effusions, primary tumors, and solid metastases

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Abstract

The objective of this study was to analyze the expression and clinical role of the high mobility group AT hook (HMGA) protein in advanced-stage serous ovarian carcinoma. HMGA2 protein expression was investigated in 199 effusions and in 50 patient-matched primary tumors and solid metastases using immunohistochemistry. Results were analyzed for association with clinicopathologic parameters, including chemotherapy response, and survival. HMGA2 was expressed in tumor cells in 94.5 %, 96 %, and 90 % of specimens, respectively. There was no difference in HMGA2 expression between patient-matched samples from different anatomic sites (p > 0.3). HMGA2 expression in chemo-naïve samples was significantly higher in older patients (p = 0.006, p = 0.01, and p = 0.005 for effusions, primary tumors, and solid metastases, respectively). No association was found with residual disease volume. Furthermore, HMGA2 expression was not associated with FIGO stage (p > 0.2), except in chemo-naïve effusions (n = 106, p = 0.016). There was no difference in HMGA2 expression between chemo-naïve samples and samples obtained post-chemotherapy in effusions (p = 0.2) or primary tumors (p = 0.1). However, solid metastases obtained after chemotherapy exposure had higher HMGA2 expression compared with chemo-naïve samples (p = 0.032). HMGA2 expression was unrelated to chemotherapy response or survival. However, it was directly related to protein expression of the previously studied cancer stem cell marker Nestin (p = 0.01) and the gap junction protein claudin-7 (p = 0.02) and inversely related to the mRNA level of the E-cadherin repressor SIP1 (p = 0.02). This study provides evidence that HMGA2 is universally expressed in advanced-stage ovarian serous carcinoma irrespective of anatomic site, suggesting that HMGA2 may have a clinical role as therapeutic target.

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Financial acknowledgment

This work was supported by the Inger and John Fredriksen Foundation for Ovarian Cancer Research, the Norwegian Cancer Society, and the Research Foundation at the Norwegian Radium Hospital. Thea Eline Hetland is the recipient of a PhD scholarship from the Health Region South-Eastern Norway.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, 0424, Oslo, Norway

    Thea Eline Hetland, Janne Kærn & Claes G. Tropé

  2. Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, 0424, Oslo, Norway

    Arild Holth, Vivi Ann Flørenes & Ben Davidson

  3. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0424, Oslo, Norway

    Claes G. Tropé & Ben Davidson

  4. Faculty of Health Sciences, Oslo University College, 0130, Oslo, Norway

    Vivi Ann Flørenes

  5. Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310, Oslo, Norway

    Ben Davidson

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  1. Thea Eline Hetland
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Correspondence to Ben Davidson.

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Hetland, T.E., Holth, A., Kærn, J. et al. HMGA2 protein expression in ovarian serous carcinoma effusions, primary tumors, and solid metastases. Virchows Arch 460, 505–513 (2012). https://doi.org/10.1007/s00428-012-1228-9

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  • DOI: https://doi.org/10.1007/s00428-012-1228-9

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