Daniel Bulzico1,2, Paulo Antônio Silvestre de Faria3, Camila Bravo Maia3, Marcela Pessoa de Paula4, Davi Coe Torres5, Gerson Moura Ferreira6, Bruno Ricardo Barreto Pires6, Rocio Hassan5, Eliana Abdelhay6, Mario Vaisman7, Leonardo Vieira Neto4,7. 1. Endocrine Oncology Unit, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil. danielbulzico@gmail.com. 2. Endocrinology Section, Federal Hospital of Lagoa, Rio de Janeiro, Brazil. danielbulzico@gmail.com. 3. Division of Pathology, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil. 4. Endocrinology Section, Federal Hospital of Lagoa, Rio de Janeiro, Brazil. 5. Laboratory of Oncovirology, Center for Bone Marrow Transplants, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil. 6. Stem cell Laboratory, Center for Bone Marrow Transplants, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil. 7. Department of Internal Medicine and Endocrinology Section, Medical School and Clementino Fraga Filho University Hospital, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.
Abstract
PURPOSE: Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed. METHODS: The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated. RESULTS: Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r s = 0.44, p < 0.001); SIP1 (r s = 0.51, p < 0.001); and SNAIL (r s = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r s = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05). CONCLUSIONS: Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.
PURPOSE: Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed. METHODS: The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated. RESULTS: Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r s = 0.44, p < 0.001); SIP1 (r s = 0.51, p < 0.001); and SNAIL (r s = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r s = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05). CONCLUSIONS:Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.
Authors: M Reincke; M Karl; W H Travis; G Mastorakos; B Allolio; H M Linehan; G P Chrousos Journal: J Clin Endocrinol Metab Date: 1994-03 Impact factor: 5.958
Authors: Bruno R B Pires; Renata Binato; Gerson M Ferreira; Stephany Corrêa; Bárbara Du Rocher; Daniel Bulzico; Susanne Crocamo; Everton Cruz Dos Santos; Luize G Lima; Eliana Abdelhay Journal: Int J Mol Sci Date: 2021-11-10 Impact factor: 5.923
Authors: Dipranjan Laha; Robert R C Grant; Prachi Mishra; Myriem Boufraqech; Min Shen; Ya-Qin Zhang; Matthew D Hall; Martha Quezado; Michelly Sampaio De Melo; Jaydira Del Rivero; Martha Zeiger; Naris Nilubol Journal: J Exp Clin Cancer Res Date: 2022-09-23