Role of IL-12p40 in cervical carcinoma

Br J Cancer. 2012 Dec 4;107(12):1956-62. doi: 10.1038/bjc.2012.488. Epub 2012 Oct 25.

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).

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin-12 Subunit p35 / metabolism
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-12 Subunit p40 / metabolism*
  • Interleukin-17 / metabolism
  • Interleukin-23 Subunit p19 / metabolism
  • Interleukin-6 / metabolism
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Interleukin-12 Subunit p35
  • Interleukin-12 Subunit p40
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • Interleukin-6
  • RNA, Messenger