{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:26:04Z","timestamp":1760239564566,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Center of Portuguese Oncology Institute of Porto","award":["CI-IPOP-19-2016","CI-IPOP-82-2017","Projecto Estrat\u00e9gico UID\/DTP\/00776\/POCI-01-0145-FEDER-006868"],"award-info":[{"award-number":["CI-IPOP-19-2016","CI-IPOP-82-2017","Projecto Estrat\u00e9gico UID\/DTP\/00776\/POCI-01-0145-FEDER-006868"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/143717\/2019"],"award-info":[{"award-number":["SFRH\/BD\/143717\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liga Portuguesa Contra o Cancro\/Funda\u00e7\u00e3o PT","award":["LPCC\/Nacional-2020"],"award-info":[{"award-number":["LPCC\/Nacional-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others. Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry. Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse. Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy.<\/jats:p>","DOI":"10.3390\/jcm9123911","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T07:49:54Z","timestamp":1606895394000},"page":"3911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer"],"prefix":"10.3390","volume":"9","author":[{"given":"Rita","family":"Silva-Oliveira","sequence":"first","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira n. 228, 4050-313 Porto, Portugal"}]},{"given":"Filipa Ferreira","family":"Pereira","sequence":"additional","affiliation":[{"name":"Breast Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Sara","family":"Petronilho","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Ana Teresa","family":"Martins","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-6356","authenticated-orcid":false,"given":"Ana","family":"Lameirinhas","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Vera","family":"Const\u00e2ncio","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-1197","authenticated-orcid":false,"given":"In\u00eas","family":"Caldas-Ribeiro","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-1263","authenticated-orcid":false,"given":"Sofia","family":"Salta","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Paula","family":"Lopes","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira n. 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-0711","authenticated-orcid":false,"given":"Lu\u00eds","family":"Antunes","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Group\u2014Research Center &amp; Department of Epidemiology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Fernando","family":"Castro","sequence":"additional","affiliation":[{"name":"Breast Cancer Clinic and Department of Surgical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Susana Palma","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Breast Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira n. 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira n. 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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