PIK3CA amplification associates with resistance to chemotherapy in ovarian cancer patients.
PI3K/AKT signalling pathway controls important cellular processes such as the cell proliferation and apoptosis. PIK3CA gene encoding a catalytic subunit of the PI3K is mutated and/or amplified in various neoplasms, including ovarian cancer. We aimed to evaluate PIK3CA alterations and their clinical importance in ovarian cancer patients. Molecular analysis was performed on 117 ovarian carcinomas with the use of qPCR, SSCP and sequencing. In a group of 98 patients with complete clinical data, 62 patients were treated with standard taxane-platinum regimens and 36 patients with platinum-cyclophosphamide regimens. A multivariate analysis was performed by the Cox's and logistic regression models. PIK3CA mutations occurred in 5/117 (4.3%) carcinomas, exclusively in the endometrioid and clear cell types (p = 0.0002); they were also associated with low FIGO stage (p = 0.0003), low tumor grade (p = 0.045) and early patient's age at diagnosis (p = 0.0005). The PIK3CA amplification (predominantly a low-level) was found in 28/117 (24%) ovarian carcinomas. It was more frequent in TP53 mutant tumors (p = 0.012) and tended to associate with high pAKT expression (p = 0.061). The PIK3CA amplification strongly diminished odds of complete remission (OR = 0.25, p = 0.033) and platinum sensitive response (PS, OR = 0.12, p = 0.004) in the taxane-platinum treated patients. The odds of PS were also much lower in all patients with the PIK3CA amplification evaluated together, regardless of the treatment applied (OR = 0.18, p = 0.001). Our results suggest that PIK3CA amplification may be a marker predicting ovarian cancer response to chemotherapy.
Kolasa
Iwona K
IK
Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Rembiszewska
Alina
A
Felisiak
Anna
A
Ziolkowska-Seta
Izabela
I
Murawska
Magdalena
M
Moes
Joanna
J
Timorek
Agnieszka
A
Dansonka-Mieszkowska
Agnieszka
A
Kupryjanczyk
Jolanta
J
D019943:Amino Acid Substitution; D002945:Cisplatin / Q000627:therapeutic use; D058534:Class I Phosphatidylinositol 3-Kinases; D003062:Codon; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons; D005260:Female; D005784:Gene Amplification; D005819:Genetic Markers; D006801:Humans; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests
D003062:Codon; D005819:Genetic Markers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D002945:Cisplatin