Caracterización de la respuesta inmunitaria-inflamatoria en el cuello uterino en pacientes con displasias de cervix

  1. Callejas de Valero, Diana Estela
Supervised by:
  1. Melchor Álvarez de Mon Soto Director
  2. Jesús Alberto Mosquera Sulbarán Co-director

Defence university: Universidad de Alcalá

Fecha de defensa: 21 July 2011

  1. Agustín Albillos Martínez Chair
  2. David Díaz Martín Secretary
  3. Nereida Valero Cedeño Committee member
  4. María Kiriakidis Longhi Committee member
  5. José Antonio Girón González Committee member
  1. Medicina y Especialidades Médicas

Type: Thesis


Introduction: Uterine cervix cancer is one of the most prevalent pathologies in the world. According to Health World Organization is the second cause of mortality by cancer in women. Molecular studies have shown the association between intraepithelial neoplasia and human papilloma virus (HPV) infection, suggesting a role of this virus in the progression of cervix intraepithelial lesions. Aims: To determine the cytokine and growth factor profiles in uterine cervix of patients with intraepithelial dysplasia and their association with dysplasia grades and HPV infection. Materials and Methods: Four groups of patients (n= 183) were studied in different periods of time and obtained from a population of 500 women from different health centers. Controls are uterine cervix samples from healthy women.Tissue expression of cytokine and growth factors (TNF-α, IL-2, IL-4, IL-6, IL-10, IL-2R, GMCSF, TGF-β1 and VEGF) were determined by indirect immunofluorescence and HPV infection by polymerase chain reaction. Cells were counted in stroma and epithelial zones and the mean±SD in X400 field was obtained. Statistical analysis was performed comparing means of patients vs. control and means of cytokine expression vs. HVP infection. Results: Increased IFN-γ, TNFα, IL-6, IL-10, GMCSF, TGF-β and VEGF expressions in the intraepithelial lesions were observed. Increments of IFN-γ, TGF-β, VEGF were related to dysplasia grades. IL-2 expression was found decreased and its receptor (IL-2R) increased related to dysplasia grades. IL-4 remained unaltered. HVP infection was not associated to the expression of cytokines and growth factors. Conclusions: The present study showed a heterogeneous cytokine and growth factor profiles, may be related to progression or inhibitions of intraepithelial neoplasia. The role of HVP infection was not relevant in these profiles, suggesting that the local immune response to the neoplasia was predominant to the modulation by external factors such as viral infection.