[논문]Expression of Toll-like Receptor 9 Increases with Progression of Cervical Neoplasia in Tunisian Women - A Comparative Analysis of Condyloma, Cervical Intraepithelial Neoplasia and Invasive Carcinoma

Fehri, Emna; Ennaifer, Emna; Ardhaoui, Monia; Ouerhani, Kaouther; Laassili, Thalja; Rhouma, Rahima Bel Haj; Guizani, Ikram; Boubaker, Samir

doi:10.7314/apjcp.2014.15.15.6145

[해외논문] Expression of Toll-like Receptor 9 Increases with Progression of Cervical Neoplasia in Tunisian Women - A Comparative Analysis of Condyloma, Cervical Intraepithelial Neoplasia and Invasive Carcinoma 원문보기

Asian Pacific journal of cancer prevention : APJCP, v.15 no.15, 2014년, pp.6145 - 6150

Fehri, Emna (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Ennaifer, Emna (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Ardhaoui, Monia (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Ouerhani, Kaouther (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Laassili, Thalja (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Rhouma, Rahima Bel Haj (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Guizani, Ikram (HPV Unit Research. Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases) , Boubaker, Samir (Department of Human and Experimental Pathology, Pasteur Institute of Tunis)

Abstract ▼ AI-Helper

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

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제안 방법

Red or purple-red color in the cytoplasm of cells was defined as TLR9 positive staining. Based on the staining intensity and the distribution and the proportion of TLR9 positive cells in squamous epithelium, TLR9 immunoreactivity was scored on a scale from 0 to 4+ as follow: 0: no positive staining cells; 1+: less than 50% of cells with weak intensity; 2+: more than 50% of cells with moderate intensity; 3+: more than 50% of cells with strong intensity; 4+ : more than 80% of cells with very strong intensity.
,2014). The present study aims to evaluate the expression levels of TLR9 on Tunisian cervical samples in gradual stages of CINs and ISCC using normal cervical tissues and condyloma as control cases.
Two histopathologists blindly reviewed the slides and evaluated the immunohistochemical data under light microscopy with photography. Red or purple-red color in the cytoplasm of cells was defined as TLR9 positive staining.

대상 데이터

53 archival (2008-2012) formalin fixed and paraffin-embedded tissues derived from cervical biopsies, conization or hysterectomy specimens collected from the files of the Department of Human and Experimental Pathology of Pasteur Institute of Tunis and five departments of pathology from the Northern, Central and Southern Tunisian hospitals were used in this study. All tissue sections were rechecked for pathological assessment of diagnosis in the Laboratory of Human and Experimental Pathology of Pasteur Institute of Tunis before the immunohistochemical assay.
All tissue sections were rechecked for pathological assessment of diagnosis in the Laboratory of Human and Experimental Pathology of Pasteur Institute of Tunis before the immunohistochemical assay. Eighteen subjects were diagnosed with different stages of CIN, including 5 CIN1, 6 CIN2, 7 CIN3 and were compared to 22 cases of ISCC, 7 condyloma and 6 samples of normal cervical squamous epithelium to serve as control cases.

성능/효과

, 2012). In this series, immunohistochemical scoring of TLR9 staining using a monoclonal antibody has shown that TLR9 expression is detected in all condyloma, CINs and ISCC with a significant gradual increasing level of expression from CIN1 to ISCC. Staining was weak in 80% of the CIN1 and moderate in 83.
, 2014). Our results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patient and could represent a useful biomarker for malignant transformation of cervical cells.
Statistical analysis of the immunostaining scores of TLR9 in the different cervical samples using the non parametric kruskall-Wallis test (Table1) showed a significant increasing from normal cervical tissue to condyloma, CINs and ISCC, from condyloma to CIN3 and ISCC and from CIN1 and CIN2 to ISCC (p<0.05).
The mean scores of TLR9 expression in normal cervical epithelia, condyloma, CIN1, CIN2, CIN3 and ISCC were compared with the Kruskal-Wallis test (p<0.05).

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