HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

Journal of Translational Medicine

Ekaterina S Jordanova¹  Gert Jan Fleuren¹  Alexander AW Peters²  Vivian M Spaans¹ 

[1] Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300, RC, Leiden, the Netherlands;Department of Obstetrics and Gynaecology, Leiden University Medical Center, PO Box 9600, 2300, RC, Leiden, the Netherlands

关键词: Cervical squamous cell carcinoma;    Cervical adenosquamous carcinoma;    Cervical adenocarcinoma;    Cervical cancer;    Immune escape;    Immune surveillance;    HLA-E;   

Others  :  829723
DOI  :  10.1186/1479-5876-10-184

 received in 2012-06-06, accepted in 2012-08-30,  发布年份 2012

【 摘 要 】

Background

Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival.

Methods and results

HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0.001, respectively).

Conclusion

High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies.

【 授权许可】

   
2012 Spaans et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

Figure 2 .

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