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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Uterine adenosquamous carcinoma (ASC) is a rare and aggressive cervical cancer subtype.
• The receptor tyrosine kinase KIT is a therapeutic target in some cancers, like GISTs.
• Understanding KIT's role in ASC may reveal new treatment strategies.

Purpose of the Study:

• To molecularly characterize KIT expression, activation, and alterations in uterine adenosquamous carcinoma.
• To investigate the potential of KIT as a therapeutic target in ASC.
• To assess KIT hotspot mutations and gene amplification in ASC.

Main Methods:

• Immunohistochemistry was used to detect KIT (CD117), its phosphorylated form, and stem cell factor (SCF) in 30 ASC cases.
• PCR-SSCP was employed to screen for KIT hotspot mutations (exons 9, 11, 13, 17).
• Quantitative real-time PCR assessed KIT gene amplification in CD117-positive cases.

Main Results:

• CD117 expression was detected in approximately 13% of ASC cases.
• Approximately 7% of cases showed co-expression of CD117 and SCF, leading to KIT phosphorylation/activation.
• No KIT activating mutations or gene amplification were identified, though 4q aneuploidy was present in one case.

Conclusions:

• This study is the first to evaluate KIT activation and molecular alterations in a significant series of rare ASC.
• The findings indicate an absence of KIT molecular alterations in ASC.
• KIT activation, suggested by KIT/SCF co-expression, occurs in a small proportion of ASC cases.