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Cytoplasmic expression of High mobility group A2 (HMGA2) determines survival prognoses in breast cancer patients
Heilmann T.1, Vondung F.2, Borzikowsky C.3, Krüger S.2, Elessawy M.1, Alkatout I.1, Wenners A.4, Bauer M.5, Klapper W.2, Röcken C.2, Maass N.1, Schem C.6, Trauzold A.7
1Klinik für Frauenheilkunde und Geburtshilfe des Universitätsklinikums Schleswig-Holstein, Campus Kiel, Kiel, Deutschland, 2Institut für Pathologie des Universitätsklinikums Schleswig-Holstein, Campus Kiel, Kiel, Deutschland, 3Institut für Medizinische Informatik und Statistik der Christian-Albrechts-Universität zu Kiel, Kiel, Deutschland, 4Fertility Center Kiel, Kiel, Deutschland, 5Frauenarztpraxis Ostufer, Kiel, Deutschland, 6Mammazentrum am Krankenhaus Jerusalem, Hamburg, Deutschland, 7Institut für Experimentelle Tumorbiologie der Christian-Albrechts-Universität Kiel, Kiel, Deutschland

Objective: High mobility group A proteins are involved in chromatin remodelling, thereby influencing multiple fundamental biological processes. HMGA2 has been linked to oncogenic traits among a variety of malignancies, but little is known about the value of extra-nuclear HMGA2. Therefore, we determined the prognostic implications of subcellular distribution patterns of HMGA2 in breast cancer.
Materials and methods: Nuclear and cytoplasmic HMGA2 expression was evaluated in 342 breast cancer specimens and matched with clinico-pathological parameters.
Results: The overall and cytoplasmic, but not nuclear, expression of HMGA2 correlated with better survival prognoses in our collective (HR 0.34, p = 0.001 and HR 0.34, p < 0.001, respectively). Interestingly, the protective effect of cytoplasmic HMGA2 persisted in the Luminal A and TNBC intrinsic breast cancer subgroups. Evaluating Luminal A and B subgroups jointly, only cytoplasmic, but not overall or nuclear, HMGA2 expression was associated with better survival (HR 0.42, 95% CI 0.21 - 0.86, p = 0.017), irrespective of tumor size and node status. In terms of determining its prognostic value, adding HMGA2 overall and cytoplasmic expression strengthens the prognostic selectivity of a hypothetical model based on conventional breast cancer risk factors in our collective. No predictive significance with regard to endocrine or chemoendocrine therapies was observed.
Conclusion: Unexpectedly, we found a favourable survival probability upon overall expression of HMGA2 in our breast cancer collective, which was predominantly determined by the expression of HMGA2 in the cytoplasm.