KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops

Gynecol Oncol. 2008 Nov;111(2):350-5. doi: 10.1016/j.ygyno.2008.07.011. Epub 2008 Aug 16.

Abstract

Objectives: Uterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC.

Methods: In a series of 30 cases, we studied KIT (CD117), KIT phosphorylated/activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.

Results: We observed CD117 expression in approximately 13% of cases, with approximately 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case.

Conclusions: This is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Adenosquamous / enzymology*
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / pathology
  • Enzyme Activation
  • Female
  • Gene Amplification
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation
  • Phosphorylation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Stem Cell Factor / biosynthesis
  • Stem Cell Factor / metabolism*
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Young Adult

Substances

  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit