Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

Autor(es):Mostrar menos -

Brondani, Vania Balderrama ^[1] ; Lacombe, Amanda Meneses Ferreira ^[1] ; Mariani, Beatriz Marinho de Paula ^[2] ; Montenegro, Luciana ^{[2, 3]} ; Soares, Ibere Cauduro ^{[4, 5]} ; Bezerra-Neto, Joao Evangelista ^[6] ; Tanno, Fabio Yoshiaki ^[7] ; Srougi, Victor ^[7] ; Chambo, Jose Luis ^[7] ; Mendonca, Berenice Bilharinho ^{[1, 2, 3]} ; Almeida, Madson Q. ^{[1, 2, 8]} ; Zerbini, Maria Claudia Nogueira ^[4] ; Fragoso, Maria Candida Barisson Villares ^{[1, 2, 8]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Unidade Suprarrenal, Serv Endocrinol & Metabol, Hosp Clin, Av Dr Eneas Carvalho Aguiar 155, BR-05403900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Hormonios & Genet Mol LIM 42, Av Dr Eneas Carvalho Aguiar 255, BR-05403900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Lab Sequenciamento Larga Escala SELA, Av Dr Arnaldo 455, BR-01246903 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Patol, Av Dr Arnaldo 455, BR-01246903 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Serv Anat Patol, Inst Canc Estado Sao Paulo ICESP, Av Dr Arnaldo 251, BR-01246000 Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Med, Serv Oncol, Inst Canc Estado Sao Paulo ICESP, Av Dr Arnaldo 251, BR-01246000 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Med, Serv Urol, Hosp Clin, Av Dr Eneas Carvalho Aguiar 155, BR-05403900 Sao Paulo - Brazil

^[8] Univ Sao Paulo, Fac Med, Serv Endocrinol, Inst Canc Estado Sao Paulo ICESP, Av Dr Arnaldo 251, BR-01246000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 3 FEB 2021.
• Citações Web of Science: 0

Resumo

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 >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273-0.997; p = 0.049) when compared with <= 1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229-0.852; p = 0.015) when compared with <= 2. 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, 0.111-0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140-0.790) for ZNRF3 expression >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. (AU)

• Processo FAPESP: 17/26345-5 - Avaliação de fatores prognósticos dos tumores do córtex da suprarrenal e preditivos da resposta ao tratamento com mitotano em carcinomas
• Beneficiário: Maria Candida Barisson Villares Fragoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular