High mobility group protein 2 (HMGA2) is highly expressed in a broad range of benign and malignant tumors - Abstract and research summary

Q: What is HMGA2 and what does it regulate in normal development?

HMGA2 is a key component of the enhanceosome that regulates gene transcription during organ development.

Q: How does HMGA2 expression differ between tumors and normal tissues in the analyzed dataset?

HMGA2 expression is generally higher in cancer than in normal tissues, with a substantial fraction of tumor samples showing HMGA2 positivity across varying staining strengths.

Q: What clinical associations were linked to HMGA2 high or low expression?

High HMGA2 staining was associated with more aggressive features such as invasive growth, high grade, advanced pT status, metastasis, and poorer overall survival in specific cancer types. Low HMGA2 expression was linked to microsatellite instability in colorectal cancer and HPV infection in squamous cell carcinomas.

Sep 23, 2026

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High mobility group protein 2 (HMGA2) is an essential component of the enhanceosome that regulates gene transcription during organ development, and its re-expression in adult tissues is often linked to tumor formation and progression. A tissue microarray was analyzed to assess HMGA2’s role across cancers and normal tissues, showing generally higher expression in tumors. Quantitative results describe tumor positivity rates and staining strength distribution, while specific cancer types show particularly high frequencies. Associations were found between HMGA2 staining and invasive growth, higher grade, advanced pT status, metastasis, and overall survival. Results also connect low HMGA2 levels with microsatellite instability and HPV infection. The study supports HMGA2 as a potential drug target and suggests HMGA2 immunohistochemistry utility for distinguishing neoplastic from non-neoplastic tissues across multiple organs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Introduction

HMGA2 function and regulation

HMGA2 roles in tumor biology

Clinical utility and diagnostic context

Reported IHC positivity variability

Virchows Archiv (2025) 487:183–201 [https://doi.org/10.1007/s00428-025-04142-1](https://doi.org/10.1007/s00428-025-04142-1) High mobility group protein 2 (HMGA2) is highly expressed in a broad range of benign and malignant tumors Viktoria Chirico1 · Fatih Baybars Ergüven1 · Katharina Möller1 · Florian Lutz1 · Florian Viehweger1 · Martina Kluth1 · Claudia Hube‑Magg1 · Christian Bernreuther1 · Guido Sauter1 · Andreas H. Marx2 · Ronald Simon1 · Frank Jacobsen1 · Patrick Lebok1 · Till S. Clauditz1 · Waldemar Wilczak1 · Morton Freytag1 · Viktor Reiswich1 · David Dum1 · Andrea Hinsch1 · Simon Kind1 · Andreas M. Luebke1 · Ria Schlichter1 · Sören Weidemann1 · Till Krech1,3 · Stefan Steurer1 · Christoph Fraune1,3 · Sarah Minner1 · Natalia Gorbokon1 · Maximilian Lennartz1 · Eike Burandt1 · Anne Menz1 Received: 22 November 2024 / Revised: 9 April 2025 / Accepted: 5 June 2025 / Published online: 16 June 2025 © The Author(s) 2025 Abstract High mobility group protein 2 (HMGA2) is an essential component of the enhanceosome that regulates gene transcription during organ development, and its re-expression in adult tissues is often linked to tumor formation and progression. To investigate HMGA2’s role in cancer, a tissue microarray of 18,582 samples from 154 tumor types and 608 samples from 76 normal tissues was analyzed. HMGA2 expression was generally higher in cancer than in normal tissues. Of the 15,915 tumor samples, 37.5% showed HMGA2 positivity: 12% weak, 11.5% moderate, and 13.9% strong. HMGA2 was detected in at least one case in 118 of 144 tumor categories, with strong staining in 92 categories. The frequency of HMGA2 positivity was highest in cancers of the ovary and the endometrium (52.6–92.6%), thyroidal neoplasms (53.4–95%), salivary gland neoplasms (66.7–98%), and non-seminomatous testicular germ cell tumors (73.5–93.5%) . High-level HMGA2 staining was associated with invasive tumor growth of urinary bladder cancers (p < 0.0001); high-grade, advanced pT, metastasis, and poor overall survival (p < 0.0001 each) in clear cell renal cell carcinoma (RCC); nodal metastasis in papillary RCC (p = 0.0099); as well as nodal metastasis in papillary thyroid cancer (p = 0.0063). Low HMGA2 expression was linked to microsatellite instability in colorectal cancer (p = 0.0002) and HPV infection in squamous cell carcinomas (p < 0.0001) . It is concluded that HMGA2 is highly expressed in a very broad range of tumor entities. These findings emphasize a potential role of HMGA2 as a drug target and suggest utility for HMGA2 IHC for the distinction of neoplastic from non-neoplastic tissues in several organs. Keywords HMGA2 · Immunohistochemistry · Neoplastic tissue · Drug target · Tissue microarray Introduction The high mobility group protein 2 (HMGA2) is a small protein of less than 12 kDa, which can bind to AT-rich binding sites in the DNA minor groove [1] . These bindings affect DNA conformation and modify the transcription of * Ronald Simon [r.simon@uke.de](r.simon@uke.de) 1 Institute of Pathology, University Medical Center Hamburg‐ Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany 2 Department of Pathology, Academic Hospital Fuerth, 90766 Fuerth, Germany 3 Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany numerous genes [2] . HMGA2 appears to be essential for cell growth regulation. HMGA2 knock-out in mice results in diet-induced obesity while certain HMGA2 mutations lead to unusually small-sized mice [3] . Genome-wide association studies found a relationship between the height of humans and HMGA2-linked SNPs [4–9] . HMGA2 is preferentially expressed during organogenesis while its expression is reduced in adult tissues [1, 10] . However, HMGA2 is often re-expressed in tumors, where it can promote cancer cell proliferation [11], cell motility [12], epithelial-mesenchymal transition [13–16], acquisition of cancer stem cell properties [17], and resistance to chemotherapeutic agents [18] . It is

FAQs

What is HMGA2 and what does it regulate in normal development?

HMGA2 is a key component of the enhanceosome that regulates gene transcription during organ development.

How does HMGA2 expression differ between tumors and normal tissues in the analyzed dataset?

HMGA2 expression is generally higher in cancer than in normal tissues, with a substantial fraction of tumor samples showing HMGA2 positivity across varying staining strengths.

What clinical associations were linked to HMGA2 high or low expression?

High HMGA2 staining was associated with more aggressive features such as invasive growth, high grade, advanced pT status, metastasis, and poorer overall survival in specific cancer types. Low HMGA2 expression was linked to microsatellite instability in colorectal cancer and HPV infection in squamous cell carcinomas.

Sep 23, 2026

Uploaded by Pentious