Expression Patterns and Clinical Relevance of HSP70 and Metallothionein in Triple-Negative and Luminal A Breast Cancer - A Croatian Cohort Study

Sep 22, 2026

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Metallothioneins (MTs) and heat shock protein 70 (HSP70) are central regulators of the cellular stress response and metal homeostasis, with important functions in tumor biology. This study evaluates their expression patterns and potential prognostic significance across breast cancer molecular subtypes, focusing on triple-negative breast cancer (TNBC) and Luminal A, compared with benign lesions. Ninety tissue samples were analyzed by immunohistochemistry and related to clinicopathological features and treatment outcomes.

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Article Expression Patterns and Clinical Relevance of HSP70 and Metallothionein in Triple-Negative and Luminal A Breast Cancer: A Croatian Cohort Study Sara Bili´c Kneževi´c 1,†, Tamara Guli´c 2,†, Damir Grebi´c 3,4, Mirisa Toki´c 5, Manuela Avirovi´c 6, Anita Savi´c-Vukovi´c 6, Marin Marinovi´c 7, Davor Juriši´c 8 and Dalibor Brozni´c 9,10, * 1 Department of Oncology and Radiotherapy, Dubrava University Hospital, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia; [sbknezevic@kbd.hr](sbknezevic@kbd.hr) 2 Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Bra´ce Branchetta 20, 51000 Rijeka, Croatia; [tamara.gulic@uniri.hr](tamara.gulic@uniri.hr) 3 Department of General and Oncological Surgery, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia; [damir.grebic@uniri.hr](damir.grebic@uniri.hr) 4 Department of Surgery, Faculty of Medicine, University of Rijeka, Bra´ce Branchetta 20, 51000 Rijeka, Croatia 5 Department of Oncology and Nuclear Medicine, General Hospital Zadar, Bože Periˇci´ca 5, 23000 Zadar, Croatia; [mirisa.tokic@bolnica-zadar.hr](mirisa.tokic@bolnica-zadar.hr) 6 Department of General Pathology and Pathologic Anatomy, Faculty of Medicine, University of Rijeka, Bra´ce Branchetta 20, 51000 Rijeka, Croatia; [manuela.avirovic@uniri.hr](manuela.avirovic@uniri.hr) (M.A.); [anitasv@uniri.hr](anitasv@uniri.hr) (A.S.-V.) 7 Department of Traumatology, Faculty of Medicine, University of Rijeka, Bra´ce Branchetta 20, 51000 Rijeka, Croatia; [marin.marinovic1@uniri.hr](marin.marinovic1@uniri.hr) 8 Department of Plastic and Reconstructive Surgery, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia; [dr.davor.jurisic@gmail.com](dr.davor.jurisic@gmail.com) 9 Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Bra´ce Branchetta 20, 51000 Rijeka, Croatia 10 Department of Environmental Health, Teaching Institute of Public Health of Primorje-Gorski Kotar County, Krešimirova 52a, 51000 Rijeka, Croatia * Correspondence: [dalibor.broznic@uniri.hr](dalibor.broznic@uniri.hr)[ ](dalibor.broznic@uniri.hr)† The authors contributed equally to this work. Highlights What are the main findings? • Nuclear expression of HSP70 is significantly higher in malignant breast cancer specimens than in benign lesions, regardless of molecular subtype. • Cytoplasmic expression of metallothionein is significantly lower in TNBC and Luminal A carcinomas, without independent prognostic value. What are the implications of the main findings? Academic Editor: GyörgyiM ˝uzes Received: 17 January 2026 Revised: 29 January 2026 Accepted: 13 February 2026 Published: 15 February 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. • HSP70 and metallothionein expression patterns reflect cellular adaptation to stress rather than serving as independent prognostic biomarkers in breast cancer. • The results emphasize the importance of protein subcellular localization and an integrative approach in breast cancer biomarker research. Abstract Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas) . A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment ou

FAQs

What did the study find about HSP70 and metallothionein expression in malignant vs benign breast tissue?

Nuclear HSP70 expression was higher in malignant specimens than in benign lesions. Cytoplasmic metallothionein expression was lower in TNBC and Luminal A carcinomas.

Did HSP70 or metallothionein expression act as independent prognostic biomarkers?

No. Although the proteins reflect cellular adaptation to stress, HSP70 and metallothionein expression did not show independent prognostic value in multivariate models.

How were the protein expression patterns measured and linked to clinical outcomes?

Expression of MTs in cytoplasm and nucleus and HSP70 in the nucleus was assessed by immunohistochemistry, then correlated with clinicopathological features and treatment outcomes.

Sep 22, 2026

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