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.
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.
Authors: Olga Martinho; Renato Silva-Oliveira; Vera Miranda-Gonçalves; Carlos Clara; José Reynaldo Almeida; André Lopes Carvalho; João Taborda Barata; Rui Manuel Reis Journal: Transl Oncol Date: 2013-04-01 Impact factor: 4.243
Authors: Adhemar Longatto-Filho; Céline Pinheiro; Olga Martinho; Marise A R Moreira; Luiz F J Ribeiro; Geraldo S Queiroz; Fernando C Schmitt; Fátima Baltazar; Rui M Reis Journal: BMC Cancer Date: 2009-06-29 Impact factor: 4.430
Authors: Olga Martinho; Renato Silva-Oliveira; Fernanda P Cury; Ana Martins Barbosa; Sara Granja; Adriane Feijó Evangelista; Fábio Marques; Vera Miranda-Gonçalves; Diana Cardoso-Carneiro; Flávia E de Paula; Maicon Zanon; Cristovam Scapulatempo-Neto; Marise A R Moreira; Fátima Baltazar; Adhemar Longatto-Filho; Rui Manuel Reis Journal: Theranostics Date: 2017-01-15 Impact factor: 11.556