HMGA2 as a Diagnostic and Prognostic Biomarker

HMGA2 (High Mobility Group AT-hook 2) is a non-histone chromatin-binding protein that plays a key role in the regulation of gene transcription by altering chromatin structure. It is predominantly expressed during embryogenesis and is largely absent in normal adult tissues. Because HMGA2 is frequently re-expressed in cancer, HMGA2 has been suggested as a potential biomarker and therapeutic target in cancer. However, published work on HMGA2 expression in cancer have yielded highly controversial data, most likely due to the different staining protocols, antibodies, and thresholds to determine positivity.

To clarify the potential utility of HMGA2 IHC in cancer, researchers from the University of Hamburg have now successfully analyzed formalin fixed archival tissues from 76 different types of normal tissues and 15,915 tumor tissue samples from 144 different tumour types by immunohistochemistry [1]. They used a novel monoclonal rabbit recombinant antibody (HMV314) provided by our partners from ardoci GmbH. HMV314 was thoroughly validated for specificity according to the guidelines of the International Working group for Antibody Validation in the course of their study. These data make HMV314 the best validated HMGA2 antibody in the market.

The study by Chirico et al. [1], provides a comprehensive database on HMGA2 expression in human cancers. The authors demonstrate that HMGA2 can be expressed in a broad range of different tumour types (118 of 144 positive). The frequency of HMGA2 positivity was particularly high in cancers of the ovary, the endometrium, and the bilio-pancreatic system, neoplasms of salivary glands and the thyroid, as well as in testicular non-seminomatous germ cell tumors. Chirico et al. also found evidence for a poor prognosis in case of high HMGA2 expression in several tumor entities, especially in clear cell renal cell carcinoma. Moreover, the authors futher corroborated the concept of a considerable diagnostic utility of HMGA2 IHC for the distinction of neoplastic from non-neoplastic disease in many different tissue types.

The data from Chirico et al. [1] have been compiled into informative graphical representations on the MSVA website in the section: Compatibility of Antibodies. Most relevant data have been compiled into graphical representations enabling a rapid overview on HMGA2 expression in tumor cells of different kinds of cancers.

[1]   Chiriko et al. (2025): High mobility group protein 2 (HMGA2) is highly expressed in a broad range of benign and malignant tumors. Virchow Arch., online first, https://doi.org/10.1007/s00428-025-04142-1