title: Differences in cytokine mRNA profiles between premalignant and malignant lesions of the uterine cervix.
abstract: The aim of this study was to assess the expression of cytokine transcripts, reflecting the type of ongoing immune responses at the site of human papillomavirus (HPV) infection, in relation to the development of cervical neoplasia. To this end reverse transcription-polymerase chain reaction (RT-PCR) was performed for interferon (IFN) gamma, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12 (p35 and p40), and transforming growth factor (TGF beta 1) in snap-frozen cervical biopsies, which were tested for the presence of high risk HPV DNA and histologically classified from normal to invasive carcinoma (n = 40). IFN gamma, IL-10 and IL-12 (p35 and p40) transcripts were found to be expressed at significantly lower frequencies in invasive carcinoma as compared with premalignant biopsies (P = 0.006, P = 0.007 and P = 0.002, respectively). IFN gamma IL-10 mRNA were associated with the presence of the IL-12 p35 and p40 transcripts (P = 0.008 and P < 0.00001, respectively). These results are consistent with a locally reduced cellular (type 1) immunity correlating with HPV-induced invasive cervical carcinoma.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: T D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: H J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: A J
authors.initials: AJ
authors.lastname: van den Muysenberg
authors.forename: J W
authors.initials: JW
authors.lastname: van Oostveen
authors.forename: M J
authors.initials: MJ
authors.lastname: Stukart
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: N
authors.initials: N
authors.lastname: van der Vange
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000328:Adult; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism*
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger