Utility of expression of 4-hydroxynonenal tested by immunohistochemistry for cervical cancer

Abstract

Introduction: Cervical cancer (CC) is a leading cause of mortality in women around the world, with the highest incidence rate still being in developing countries. The most common aetiological factor is infection with high-risk human papilloma virus viral strains. Oxidative stress through generation of reactive oxygen species leads to lipid peroxidation and DNA damage. Studies show that reactive lipid electrophiles such as 4-hydroxynonenal (4-HNE) produced in the process play an important role in cancer signalling pathways and are a good biomarker for oxidative stress. We aim to investigate the prognostic role of 4-HNE as a biomarker for oxidative stress in patients in early and advanced stages of CC measured by immunohistochemistry.

Material and methods: This is a retrospective study of 69 patients treated at our Department of Oncogynaecology. Paraffin embedded tumour tissues were immunohistochemically tested for the levels of expression of 4-HNE. The results for H-score, Allred score, and combined score were investigated for association with tumour size, lymph node status, andInternational Federation of Gynaecology and Obstetrics stage.

Results: 4-hydroxynonenal showed higher expression in more advanced stages of CC and in cases with involved lymph nodes. Tumour size was not associated with the levels of 4-HNE.

Conclusions: To best of our knowledge, this is the first study to use immunohistochemistry to examine the expression of 4-HNE as a prognostic factor in CC. The 3 score systems showed similar results. The pattern of 4-HNE histological appearance is dependent on the histological origin of cancer and is not universal.

Keywords: 4-HNE; ROS; cervical cancer; lipid metabolism; oxidative stress.

Fig. 1

Immunohistochemistry staining with 4-hydroxynonenal in cervical squamous cell carcinoma: cytoplasmic positivity absent (A), weak (B), and moderate (C) intensity in tumour cells; strong intensity in immune cells (A, B 400×)

Fig. 2

Kruskal-Wallis test for association between tumour-node-metastasis T stage and H-score (A), T stage and H-score in node-negative and node-positive patients (B) FIGO stage and H-score (C), N stage and H-score (D) FIGO – International Federation of Gynaecology and Obstetrics

Fig. 3

Kruskal-Wallis test for association between tumour node metastasis T stage and Allred score (A), T stage and Allred score in node-negative and node-positive patients (B), FIGO stage and Allred score (C), N stage and Allred score (D) FIGO – International Federation of Gynaecology and Obstetrics

Fig. 4

Kruskal-Wallis test for association between tumour-node-metastasis T stage and combined score (A), T stage and combined-score in node negative and node positive patients (B), FIGO stage and combined score (C), N stage and combined score (D) FIGO – International Federation of Gynaecology and Obstetrics