Enhanced expression of hedgehog signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions

Mod Pathol. 2006 Aug;19(8):1139-47. doi: 10.1038/modpathol.3800600. Epub 2006 Jun 16.

Abstract

The hedgehog (Hh)-signaling pathway plays an essential role in normal development. Deregulation of this pathway is responsible for several types of cancers. The aim of this study was to determine the expression pattern and the extent of Hh-signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions. A total of 106 uterine cervical cancers and related lesions (37 squamous cell carcinomas, 23 cervical intraepithelial neoplasia (CIN) III, 10 CIN II, four CIN I, 32 normal cervical epithelia) were immunohistochemically analyzed with anti-Shh, Indian Hh (Ihh), Patched (PTCH), Smoothened (Smo), Gli-1, Gli-2, Gli-3 antibodies on paraffin blocks. The results showed that the expression of all the Hh-signaling molecules was greatly enhanced in uterine cervical tumors, including carcinoma and its precursor lesions. The staining pattern was mainly cytoplasmic except for Gli-1/2, whose expression was observed in both cytoplasm and nucleus. In case of Ihh, PTCH, Smo and Gli-1, their expression in normal epithelium was completely absent or rare. The expression of all the seven Hh-signaling molecules mentioned above was significantly increased in CIN II/III and carcinoma, compared with that in normal epithelium (P < 0.05). The expression of Shh was increased by double; the first increase occurred in normal epithelium-CIN transition, and the second, during the progression of CIN to carcinoma. These results strongly suggest that the Hh-signaling pathways were extensively activated in carcinoma and CIN of uterine cervix. In conclusion, the Hh-signaling pathways may be involved in carcinogenesis of squamous cell carcinoma of uterine cervix and can be considered as a potential therapeutic target.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cervical Intraepithelial Neoplasia / metabolism*
  • Cervical Intraepithelial Neoplasia / pathology
  • Disease Progression
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hedgehog Proteins
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Signal Transduction
  • Tissue Array Analysis
  • Trans-Activators / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Hedgehog Proteins
  • SHH protein, human
  • Trans-Activators