{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:07:15Z","timestamp":1794017235364,"version":"4.8.0"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023652","name":"University of Rijeka","doi-asserted-by":"crossref","award":["uniri-iskusni-biomed-23-185"],"award-info":[{"award-number":["uniri-iskusni-biomed-23-185"]}],"id":[{"id":"10.13039\/501100023652","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100023652","name":"University of Rijeka","doi-asserted-by":"crossref","award":["uniri-iz-25-45"],"award-info":[{"award-number":["uniri-iz-25-45"]}],"id":[{"id":"10.13039\/501100023652","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research.<\/jats:p>","DOI":"10.3390\/cells15040351","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:37:28Z","timestamp":1771245448000},"page":"351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression Patterns and Clinical Relevance of HSP70 and Metallothionein in Triple-Negative and Luminal A Breast Cancer: A Croatian Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Sara","family":"Bili\u0107 Kne\u017eevi\u0107","sequence":"first","affiliation":[{"name":"Department of Oncology and Radiotherapy, Dubrava University Hospital, Avenija Gojka \u0160u\u0161ka 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-1728","authenticated-orcid":false,"given":"Tamara","family":"Guli\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3715-2254","authenticated-orcid":false,"given":"Damir","family":"Grebi\u0107","sequence":"additional","affiliation":[{"name":"Department of General and Oncological Surgery, Clinical Hospital Center Rijeka, Kre\u0161imirova 42, 51000 Rijeka, Croatia"},{"name":"Department of Surgery, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirisa","family":"Toki\u0107","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine, General Hospital Zadar, Bo\u017ee Peri\u010di\u0107a 5, 23000 Zadar, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6601-7521","authenticated-orcid":false,"given":"Manuela","family":"Avirovi\u0107","sequence":"additional","affiliation":[{"name":"Department of General Pathology and Pathologic Anatomy, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-5269","authenticated-orcid":false,"given":"Anita","family":"Savi\u0107-Vukovi\u0107","sequence":"additional","affiliation":[{"name":"Department of General Pathology and Pathologic Anatomy, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marin","family":"Marinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-6963","authenticated-orcid":false,"given":"Davor","family":"Juri\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Clinical Hospital Center Rijeka, Kre\u0161imirova 42, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3935-5338","authenticated-orcid":false,"given":"Dalibor","family":"Brozni\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"},{"name":"Department of Environmental Health, Teaching Institute of Public Health of Primorje-Gorski Kotar County, Kre\u0161imirova 52a, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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