KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops.
OBJECTIVE
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.
Martinho
Olga
O
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Gonçalves
Alberto
A
Moreira
Marise A R
MA
Ribeiro
Luiz F J
LF
Queiroz
Geraldo S
GS
Schmitt
Fernando C
FC
Reis
Rui M
RM
Longatto-Filho
Adhemar
A
D000328:Adult; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit