{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:47:57Z","timestamp":1768420077648,"version":"3.49.0"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/26345-5"],"award-info":[{"award-number":["2017\/26345-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of &gt;1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273\u20130.997; p = 0.049) when compared with \u22641.5; for ZNRF3 expression &gt;2, the HR for OS was 0.441 (95% CI, 0.229\u20130.852; p = 0.015) when compared with \u22642. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111\u20130.932) for ATRX expression &gt;2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140\u20130.790) for ZNRF3 expression &gt;2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.<\/jats:p>","DOI":"10.3390\/ijms22031238","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"1238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma"],"prefix":"10.3390","volume":"22","author":[{"given":"Vania Balderrama","family":"Brondani","sequence":"first","affiliation":[{"name":"Unidade de Suprarrenal, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda Meneses Ferreira","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Marinho de Paula","family":"Mariani","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 255, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 255, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Laborat\u00f3rio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 455, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iber\u00ea Cauduro","family":"Soares","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 455, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 251, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Evangelista","family":"Bezerra-Neto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 251, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio Yoshiaki","family":"Tanno","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Srougi","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luis","family":"Chambo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-1084","authenticated-orcid":false,"given":"Berenice Bilharinho","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 255, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Laborat\u00f3rio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 455, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madson Q.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 255, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Servi\u00e7o de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 251, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-9816","authenticated-orcid":false,"given":"Maria Claudia Nogueira","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 455, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Candida Barisson Villares","family":"Fragoso","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 155, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as de Carvalho Aguiar, 255, S\u00e3o Paulo 05403-900, Brazil"},{"name":"Servi\u00e7o de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo, Av. Dr. Arnaldo, 251, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s00268-001-0030-7","article-title":"Adrenal cortical carcinoma","volume":"25","author":"Dackiw","year":"2001","journal-title":"World J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1007\/s00268-005-0329-x","article-title":"Extent of disease at presentation and outcome for adrenocortical carcinoma: Have we made progress?","volume":"30","author":"Kebebew","year":"2006","journal-title":"World J. 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