title: Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy.
abstract: We evaluated the association between epithelial-mesenchymal transition (EMT)-derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 ± 10 years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty-six percent of the patients were positive for human papilloma virus. Median progression-free survival (PFS) was 6.6 months (95% confidence interval [CI]: 4.0-9.1, whereas overall survival (OS) was 30.0 months (95% CI: 11-48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P = 0.002), epidermal growth factor receptor (EGFR) (P = 0.001), and TWIST2 (P = 0.001) expression levels, as well as a tumor size <6 cm (P = 0.02), influenced OS. Changes in TWIST2 levels and loss of E-cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P = 0.0001), as those with loss of E-cadherin (P = 0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E-cadherin: median 14 months, 95% CI: 3-24; negative EGFR + positive E-cadherin: median 31 months, 95% CI: 14-NA; P = 0.02.). The presence of EMT markers was associated with proliferative and pro-angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer.
authors.affiliation: Clinical Oncology Group, Centro Javeriano de Oncología, Hospital Universitario San Ignacio (HUSI), Bogotá, Colombia.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rojas-Puentes
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Cardona
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Hernán
authors.initials: H
authors.lastname: Carranza
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vargas
authors.affiliation: Department of Pathology, Hospital Universitario San Ignacio (HUSI), Bogotá, Colombia.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jaramillo
authors.affiliation: Radiotherapy Group, Centro Javeriano de Oncología, Hospital Universitario San Ignacio (HUSI), Bogotá, Colombia.
authors.forename: Delma
authors.initials: D
authors.lastname: Zea
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Cancerología de México (INCAN), México City, México.
authors.forename: Lucely
authors.initials: L
authors.lastname: Cetina
authors.affiliation: Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Wills
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Cancerología de México (INCAN), México City, México.
authors.forename: Erika
authors.initials: E
authors.lastname: Ruiz-Garcia
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Cancerología de México (INCAN), México City, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D059248:Chemoradiotherapy; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors
keywords: Angiogenesis epidermal growth factor receptor; cervical neoplasms; epithelial-mesenchymal transition; gene expression