Classical and non-classical HLA molecules and p16INK4a expression in precursors lesions and invasive cervical cancer

Gonçalves, Maria Alice Guimarães; Discorde, Magali Le; Simões, Renata Toscano; Rabreau, Michèle; Soares, Edson García; Donadi, Eduardo Antônio; Carosella, Edgardo D.

doi:10.1016/j.ejogrb.2008.06.010

Cited by 43 publications

(45 citation statements)

References 23 publications

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“…18 Several studies have demonstrated that cervical cancer tissue expressed HLA-G and that its expression correlates with tumor progression. [5][6][7][8]10 In this report, the wildtype HLA-G*01:01:01 allele conferred protection against invasive cancer, whereas variant HLA-G*01:01:02, -G*01:06 and -G*3 0 UTR 14-bp insertion alleles increased cervical cancer risk. The HLA-G*01:01:02 and -G*01:06 alleles both have a synonymous substitution (Proline) at codon 57.…”

Section: Discussionmentioning

confidence: 53%

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Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Ferguson

Ramanakumar

Koushik

et al. 2012

Intl Journal of Cancer

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Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression in tumor cells may enable them to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G polymorphism on risk of high-grade cervical intraepithelial neoplasia (HG-CIN) and cervical cancer in a Canadian population. The authors have analyzed 1,372 women from participants recruited between 2001 and 2009 in the ongoing Biomarkers of Cervical Cancer Risk case-control study. A total of 539 women with histologically confirmed HG-CIN and invasive cancer formed the case series, and 833 women with normal cytology served as controls. Cervical specimens were tested for human papillomavirus (HPV) DNA using the MY09/11 PCR protocol and HLA-G alleles where determined using a direct DNA sequencing procedures. HLA-G polymorphisms were not associated with HG-CIN or HPV infection. However, the risk for invasive cancer was significantly increased with the homozygous genotypes HLA-G*01:01:02 [odds ratio (OR) 5 3.52, 95% confidence interval (CI): 1.43-8.61, p 5 0.006], 2G*01:06 (OR 5 19.1, 95% CI: 2.29-159, p 5 0.005) and 2G* 3 0 UTR 14-bp insertion (OR 5 2.17, 95% CI: 1.10-4.27, p 5 0.020), whereas, the heterozygotic form of the G*01:01:01 wild-type allele was significantly associated with a reduced risk of invasive cancer (OR 5 0.31, 95% CI: 0.16-0.59, p < 0.0001) after adjusting for age, HPV infection and ethnicity. These associations were also observed with progression of disease from HG-CIN to invasive cancer among HPV-positive women. These results suggest that HLA-G polymorphism is an independent risk factor for the development of invasive cervical cancer.

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Section: Discussionmentioning

confidence: 53%

“…For instance, HLA-G expression in cervical cancer tissue has been found to be increased, [5][6][7] reduced, 8 or absent. 9,10 HLA-G expression has correlated positively, 6,7 negatively, 5,10 or not at all 11 with cervical disease progression.…”

mentioning

confidence: 99%

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Ferguson

Ramanakumar

Koushik

et al. 2012

Intl Journal of Cancer

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“…In contrast, HLA-E expression exhibited an opposite behavior according to SIL severity. 11 The balance between constitutive HLA-G and virus-modulated expression may determine the outcome of the infection, facilitating or not virus persistence. This study was designed to evaluate the potential involvement of polymorphic sites of the HLA-G gene in the development of SIL in women harboring HPV infection.…”

Section: Hla-g In Patients Stratified According To Lesion Severity Anmentioning

confidence: 99%

“…HLA-G transcripts are also expressed at low levels in a variety of normal human adult tissues; 10 however, normal cervical cells do not express HLA-G. 11 HLA-G expression may be upregulated in inflammatory and neoplastic tissues, 12 and in viral infections.…”

mentioning

confidence: 99%

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

et al. 2009

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Human papillomavirus (HPV) infection is etiologically associated with low-(LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/ þ 14 bp and G0104/À14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/ þ 14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.

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“…T h i s a l teration was not statistically significant, however (p=0.14). Gonclaves el al (Goncalves, Le Discorde et al 2008) also examined MHC class I expression in FFPE biopsy blocks, but in women with normal through cancerous histology. They found that HLA-A/B/C expression was not significantly elevated in HPVpositive compared to HPV-negative women (OR, 2.29; 95% CI, 0.77-11.00; P = 0.14).…”

Section: Introductionmentioning

confidence: 99%

Cytokines and Markers of Immune Response to HPV Infection

Koshiol¹,

Kovacic²

2012

Recent Advances in Immunology to Target Cancer, Inflammation and Infections

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Classical and non-classical HLA molecules and p16INK4a expression in precursors lesions and invasive cervical cancer

Cited by 43 publications

References 23 publications

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

Cytokines and Markers of Immune Response to HPV Infection

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