Epstein-Barr virus (EBV) genes expression in cervical intraepithelial neoplasia and invasive cervical cancer: A comparative study with human papillomavirus (HPV) infection

• Published in: Human pathology 2000-03, Vol.31 (3), p.318-326
• Main Authors: Sasagawa, Toshiyuki, Shimakage, Misuzu, Nakamura, Mitsuo, Sakaike, Jun, Ishikawa, Hiroshi, Inoue, Masaki
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adenocarcinoma - pathology; Adenocarcinoma - virology; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Southern; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Carrier Proteins - genetics; Carrier Proteins - metabolism; cervical cancer; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Cervix Uteri - pathology; Cervix Uteri - virology; Cytoskeletal Proteins; DNA Primers - chemistry; DNA, Viral - analysis; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens; Female; Female genital diseases; Fluorescent Antibody Technique, Indirect; Gene Expression; Gynecology. Andrology. Obstetrics; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - isolation & purification; human papillomavirus; Humans; In Situ Hybridization; Intracellular Signaling Peptides and Proteins; Japanese women; LIM Domain Proteins; Medical sciences; Middle Aged; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; RNA, Viral - analysis; RNA, Viral - genetics; RNA, Viral - metabolism; Tumors; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; uterine cervix; Viral Proteins - metabolism
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(00)80245-2

To elucidate a causative role of Epstein-Barr virus (EBV) for cervical cancer, presence and expression of EBV genes were examined in 31 cervical carcinomas (ICC), 23 cervical intraepithelial neoplasias (CIN), and 35 normal cervices (NCX). In reverse transcription polymerase chain reaction (RT-PCR) analysis, EBER-1 mRNA was expressed in 74% (23/31) of ICC, 83% (19/23) of CIN, 37% (13/35) of NCX. LMP-1 was expressed in 52% (16/31) of ICC, 70% (16/23) of CIN, and 23% (8/35) of NCX, and EBNA-2 was expressed in 32% (10/31) of ICC, in 48% (11/23) of CIN, and in 11% (4/35) of NCX. Expression rates of these genes were significantly higher in ICC and CIN than in NCX ( P < .05). RNA in situ hybridization analysis showed that EBER-1 was expressed in half (7/14) of ICC and 35% (6/17) of CIN, and BamH-W, which is a leader sequence of EBNA genes, was expressed in 86% (12/14) of ICC and 71% (12/17) of CIN. LMP-1 and EBNA-2 proteins also were detected in ICC and CIN cells by immunofluorescence staining. PCR analysis showed that EBV genome was detected in 55% (17 of 31) of ICC and in 26% (9/35) of NCX. In contrast, human papillomavirus (HPV) DNA was detected in 84% (26/31) of ICC, whereas none of NCX had HPV DNA. Either EBV or HPV was detected in 61% (19/31) of ICC, whereas both EBV and HPV was detected in 39% (12/31) of ICC. EBV infection may be involved in the development of cervical cancer, although further study should be performed to elucidate a causative role of EBV for the cancer.