title: Role of IL-12p40 in cervical carcinoma.
abstract: BACKGROUND
  Previously, we have shown that low IL-12p40 mRNA expression by cervical cancer cells is associated with a poor survival of cervical cancer patients. As IL-12p40 is both a subcomponent of interleukin (IL)-12 and IL-23, the aim of this study was to elucidate the role of IL-12p40 in cervical cancer.
  
  
  METHODS
  We have measured the expression of IL-23p19 mRNA, IL-12p35 mRNA and IL-12p40 mRNA using mRNA in situ hybridisation. The IL-1 and IL-6 were measured by immunohistochemistry.
  
  
  RESULTS
  As IL-23 is a component of the IL-17/IL-23 pathway, a pathway induced by IL-1 and IL-6 in humans, we have studied IL-1 and IL-6 expression. Only a high number of stromal IL-6-positive cells was shown to associate with poor disease-specific survival. The worst disease-specific survival was associated with a subgroup of patients that displayed a high number of IL-6-positive cells and low IL-12p40 expression (P<0.001). Both a high number of IL-6-positive cells and a high number of IL-6-positive cells, plus low IL-12p40 expression were shown to be clinicopathological parameters independent of lymph node metastasis, parametrial involvement and Sedlis score (P=0.009 and P=0.007, respectively).
  
  
  CONCLUSIONS
  Our results with IL-6 and IL-12p40 are in accordance with the hypothesis that the IL-17/IL-23 pathway has a suppressive role in cervical cancer.
authors.affiliation: Department of Gynecology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
authors.forename: H J M A A
authors.initials: HJ
authors.lastname: Zijlmans
authors.forename: S
authors.initials: S
authors.lastname: Punt
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: J B
authors.initials: JB
authors.lastname: Trimbos
authors.forename: G G
authors.initials: GG
authors.lastname: Kenter
authors.forename: A
authors.initials: A
authors.lastname: Gorter
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053765:Interleukin-12 Subunit p35 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D012333:RNA, Messenger