FGFR3, PIK3CA and BRAF Mutations in Urine Cytology Specimens.
Adnan Hasanovic, Gopakumar V Iyer, David B Solit, Hikmat Al-Ahmadie, Adriana Heguy, Oscar Lin. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Urothelial carcinoma is a common malignancy with variable biology and natural history. Prior studies have shown that the most common somatic mutations found in UC include FGFR3 and PIK3CA. The development of targeted therapies exploiting somatic mutations, translocations, and amplifications has served as a platform for new treatment protocols. This study is designed to evaluate if cytology specimens represent a suitable material to select patients for target therapy, given that urine cytology is a highly specific and relatively sensitive in the diagnosis of high grade UC and it is relatively easy to obtain. Clinico-pathological findings were also analyzed.
Design: Thirty cases of histologically proven UC and matching urine cytology material were identified at our institution. The cytology specimens were frozen, methanol fixed, cytospin unstained slides. The contents of one cytospin slide and a thick section of matching FFPE tissue were submitted to whole genome amplification. Samples were analyzed using the Sequenom platform for FGFR3, PIK3CA and BRAF mutations using probes previously validated with frozen specimens of UC. All traces for mutation findings were manually reviewed. Clinico-pathologic correlation was performed.
Results: The frequency of mutations in cytology specimens is listed in the table 1. Correlation with the tumor sections showed matching FGFR3 mutation in cytology and surgical specimen in one case, whereas 4 pairs of specimens had discordant FGFR3 mutations. Additionally, 9 cytology specimens showed the presence of a mutation (S371C) not seen in the tumor sections. Concordant PIK3CA mutation was present in both cytology and histology specimens only in one case, while 4 cases showed discrepant mutational status. BRAF was not detected in any cytology or surgical specimen. Correlation of the molecular status with the clinical findings showed that FGFR3 mutation was detected mostly in non-invasive UC with a papillary component, while PIK3CA mutation was found in superficial as well as muscle invasive UC with a papillary component.