Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia

analytical cross-sectional study

Authors

  • Lidyane Neves Miranda Universidade Federal do Rio Grande do Norte (UFRN)
  • Fernanda Priscila Santos Reginaldo Universidade Federal do Rio Grande do Norte (UFRN)
  • Daliana Maria Berenice Oliveira Souza Universidade Federal Rio Grande do Norte (UFRN)
  • Christiane Pienna Soares Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)
  • Tarsia Giabardo Alves Silva Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)
  • Keyla Borges Ferreira Rocha Universidade Federal do Rio Grande do Norte (UFRN)
  • Carlos André Nunes Jatobá Universidade Federal do Rio Grande do Norte (UFRN)
  • Eduardo Antonio Donadi Faculdade de Medicina de Ribeirão Preto (FMRP)
  • Joanlise Marco Leon Andrade Universidade Federal do Rio Grande do Norte (UFRN)
  • Ana Katherine Silveira Gonçalves Universidade Federal do Rio Grande do Norte (UFRN)
  • Janaína Cristiana Oliveira Crispim Universidade Federal do Rio Grande do Norte (UFRN)

Keywords:

HLA-G antigens, Interleukin-17, Cervix uteri, Immunohistochemistry, Cervical intraepithelial neoplasia

Abstract

CONTEXT AND OBJECTIVE: Impaired local cell immunity seems to contribute towards the pathogen-esis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and di-agnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregula-tory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. DESIGN AND SETTING: Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. METHODS: We examined HLA-G and IL-17 expression in the cervical microenvironment by means of im-munohistochemistry, and correlated these findings with clinical and pathological features. RESULTS: There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. CONCLUSION: These findings suggest that HLA-G and IL-17 expression may be an early marker for assess-ing the progression of cervical lesions.

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Author Biographies

Lidyane Neves Miranda, Universidade Federal do Rio Grande do Norte (UFRN)

BSc. Master’s Student, Department of Toxicology and Clinical Analysis, School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Fernanda Priscila Santos Reginaldo, Universidade Federal do Rio Grande do Norte (UFRN)

BSc. Postgraduate Student, Department of Toxicology and Clinical Analysis, School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Daliana Maria Berenice Oliveira Souza, Universidade Federal Rio Grande do Norte (UFRN)

MSc. Pharmacist, Department of Toxicology and Clinical Analysis, School of Pharmaceutical Sciences, Universidade Federal Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Christiane Pienna Soares, Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)

PhD. Associate Professor, Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp), Araraquara, São Paulo, Brazil.

Tarsia Giabardo Alves Silva, Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)

PhD. Researcher, Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp), Araraquara, São Paulo, Brazil.

Keyla Borges Ferreira Rocha, Universidade Federal do Rio Grande do Norte (UFRN)

PhD. Assistant Professor, Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Carlos André Nunes Jatobá, Universidade Federal do Rio Grande do Norte (UFRN)

PhD. Assistant Professor, Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

 

Eduardo Antonio Donadi, Faculdade de Medicina de Ribeirão Preto (FMRP)

PhD. Titular Professor, Division of Clinical Immunology, Faculdade de Medicina de Ribeirão Preto (FMRP), Ribeirão Preto, São Paulo, Brazil.

Joanlise Marco Leon Andrade, Universidade Federal do Rio Grande do Norte (UFRN)

PhD. Associate Professor, Department of Statistics, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Ana Katherine Silveira Gonçalves, Universidade Federal do Rio Grande do Norte (UFRN)

PhD. Associate Professor, Department of Obstetrics and Gynecology, School of Medicine, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

Janaína Cristiana Oliveira Crispim, Universidade Federal do Rio Grande do Norte (UFRN)

PhD, Associate Professor, Department of Toxicology and Clinical Analysis, School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.

References

Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1-17.

Carosella ED, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J. Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood. 2008;111(10):4862-70.

Rouas-Freiss N, Gonçalves RM, Menier C, Dausset J, Carosella ED. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci U S A. 1997;94(21):11520-5.

Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N. HLA-G: from biology to clinical benefits. Trends Immunol. 2008;29(3):125-32.

Zheng N, Wang CX, Zhang X, et al. Up-regulation of HLA-G expression in cervical premalignant and malignant lesions. Tissue Antigens. 2011;77(3):218-24.

Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235-8.

Zhang Y, Ma D, Zhang Y, et al. The imbalance of Th17/Treg in patients with uterine cervical cancer. Clin Chim Acta. 2011; 412(11-12):894-900.

Richart RM. The incidence of cervical and vaginal dysplasia after exposure to DES. JAMA. 1986;255(1):36-7.

Wright TC, Ronnett BM, Kurman RJ, Ferenczy A. Precancerous lesions of the cervix. In: Kurman RJ, Ellenson LH, Ronnett BM, editors. Blaustein’s pathology of the female genital tract. New York: Springer; 2011. p. 193-252.

Wright TC, Ronnett BM, Ferenczy A. Benign diseases of the cervix. In: Kurman RJ, Ellenson LH, Ronnett BM, editors. Blaustein’s pathology of the female genital tract. New York: Springer; 2011. p. 155-91.

Xie X, Clausen OP, Boysen M. Bag-1 expression as a prognostic factor in tongue squamous cell carcinomas. Laryngoscope. 2004;114(10):1785-90.

Lukovic L, Milasin J. Sister chromatid exchanges in patients with carcinoma in situ of cervix uteri. Cancer Genet Cytogenet. 1992;59(1):84-5.

Guimarães MC, Soares CP, Donadi EA, et al. Low expression of human histocompatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis, associated with papilloma virus (HPV). J Histochem Cytochem. 2010;58(5):405-11.

Ferguson R, Ramanakumar AV, Koushik A, et al. Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix. Int J Cancer. 2012;131(3):E312-9.

Gillio-Tos A, Bicalho Mda G, Fiano V, et al. Case-control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis. BMC Cancer. 2012;12:618.

Singer G, Rebmann V, Chen YC, et al. HLA-G is a potential tumor marker in malignant ascites. Clin Cancer Res. 2003;9(12):4460-4.

Lan C, Huang X, Lin S, et al. High density of IL-17-producing cells is associated with improved prognosis for advanced epithelial ovarian cancer. Cell Tissue Res. 2013;352(2):351-9.

Cannon MJ, Goyne HE, Stone PJ, et al. Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen. Cancer Immunol Immunother. 2013;62(5):839-49.

Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009;114(6):1141-9.

Wägsäter D, Löfgren S, Hugander A, Dimberg J. Expression of interleukin-17 in human colorectal cancer. Anticancer Res. 2006;26(6B):4213-6.

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Published

2015-07-07

How to Cite

1.
Miranda LN, Reginaldo FPS, Souza DMBO, Soares CP, Silva TGA, Rocha KBF, Jatobá CAN, Donadi EA, Andrade JML, Gonçalves AKS, Crispim JCO. Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study. Sao Paulo Med J [Internet]. 2015 Jul. 7 [cited 2025 Mar. 9];133(4):336-42. Available from: https://periodicosapm.emnuvens.com.br/spmj/article/view/1429

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