204P - Evaluation of PTEN and PIK3CA status in breast cancer for patient selection
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
V. Serra1, J. Rodon2, C.M. Aura3, A. Vivancos4, K. Stemke-Hale5, H. Hibshoosh6, Y. Wang7, S. Ramon Y Cajal3, J. Tabernero8, J. Baselga9
PTEN and PIK3CA status are potential predictors of response to PI3K-pathway inhibitors. Therefore, we searched the most reliable platform to assess both PTEN expression and PIK3CA mutations in primary and metastatic breast cancer (BC). We cross-validated the assays between different institutions. Studies were performed using four different sample sets of formalin-fixed paraffin-embedded (FFPE) breast cancers from VHUH/VHIO and from Columbia University. PTEN alterations were genotyped in 14 TNBCs by OncoscanTM platform (Affymetrix) and were correlated to immunohistochemistry (IHC). PTEN loss of heterozygosity (LOH, n = 4) with or without overlapping PTEN mutation (n = 5) was concordant to PTEN protein loss (H-Score < 60) by IHC in 7 samples (7/8, 88% concordance). PTEN protein loss by IHC was also cross-validated between two institutions. In a cohort of 12 TNBCs containing eight PTEN low samples, only two samples were discordant (2/12, 17% discordance). Paired primary versus metastatic tumors were identified to transit either way, in the PTEN assessment by IHC (2/8 paired samples, 25% transition). PIK3CA mutations by OncoscanTM were concordant to MassARRAY (Sequenom) in 4 out of 5 mutated samples within the panel of 17 BCs. The discrepancy (1/17, 6%) was likely due to differences in the sensitivity of the two assays. In another cohort of 21 BC samples, PIK3CA mutational status was cross-validated by MassARRAY at two institutions (MDACC and VHIO). Using identical, customized panels we found that only two samples were discordant because of mutant allele frequency close to the sensitivity of the assay (10%). Among 14 paired primary vs metastatic breast cancers we detected two transitions from wild type (WT) to H1047R mutation and one transition from E545K to WT (3/14, 21% transition), underscoring the need to determine PIK3CA status in metastatic lesions. The divergence evaluating PTEN and PIK3CA status between institutions was due to different scoring methodologies and to sensitivity of the assays respectively. For patient pre-screening purposes, MassARRAY and IHC can be performed at each institution both in primary and metastatic breast cancer lesions. OncoscanTM is a valid, centralized platform for evaluation of PTEN and PIK3CA genomic alterations in BC.Disclosure
Y. Wang: Yuker Wang is employee of Affymetrix Inc.
All other authors have declared no conflicts of interest.