Original article
EGFR, PIK3CA and PTEN gene status and their protein product expression in neuroblastic tumours

PI3K/AKT/mTOR pathway signalling is often upregulated in cancer, usually by the constitutional activation of growth factor receptors, amplification or mutation of PIK3CA and loss of tumour suppressor PTEN function. The way of PI3K/AKT/mTOR pathway activation in neuroblastoma (NB) is not well established.

The study was performed on paraffin-embedded tissue sections from 106 patients with NB. The aim of the study was to analyse the mutational status of EGFR (exons 18-21), PIK3CA (exons 5, 6, 10 and 21) and PTEN (all exons) genes, as well as to assess expression of their protein products by immunohistochemistry.

A novel mutation in exon 5 of PIK3CA, c.931 A>G (p.I311V), in two infantile tumours (2.7%) was identified. In addition some polymorphisms were found in all examined genes, including a novel one, c.285 A>T in PTEN. Polymorphism PIK3CA c.1060-17 C>A was significantly more frequent in extra-adrenal tumours. Polymorphism PIK3CA c.1145+54 A>G showed a tendency to be more frequent in children older than 18 months and in extra-adrenal tumours. Expression of EGFR was present in 95% of cases, PI3Kp110 in 92% of tumours and PTEN in all tumours (low in 39%) and did not correlate with the genetic alterations. EGFR and PTEN expression showed an association with tumour diffe­rentiation. Mutations in the EGFR, PIK3CA and PTEN genes are infrequent in neuroblastoma. Both newly detected mutations in exon 5 of PIK3CA occurred in very low risk neuroblastic tumours in infants. EGFR, PI3Kp110 and PTEN expression is a common feature of NB.