Mutations in PIK3CA Lymph Node-Positive Breast Carcinomas Are Associated with Luminal Immunophenotype
FI Aranda, L Sanchez-Tejada, C Alenda, G Peiro, J Segui, M Niveiro, A Paya, JB Laforga, E de Alava, J Palacios, M Martin. Hospital General Universitario, Alicante, Spain; Centro Investigación del Cáncer, Salamanca, Spain; Hospital Virgen del Rocío, Sevilla, Spain; GEICAM, Madrid, Spain
Background: PIK3CA activating mutations have been identified in a high proportion of breast carcinomas (BC) (∼25%). Mutations can activate the PI3K/Akt pathway and contribute to tumor progression. Its association with pathological markers is often contradictory. The purpose of the study was to evaluate PIK3CA mutations in a series of lymph node-positive (LNP) infiltrating BC and to correlated the results with immunohistochemical (IHC) variables and BC subtypes.
Design: A total of 391 LNPBC patients included in the GEICAM 9906 clinical trial were studied. IHC was applied on tissue microarrays for ER (cut-off 10%), PgR (cut-off 10%), Ki67 (cut-off 15%), p53 (cut-off 20%), HER2 (all 2+ and <30% 3+ confirmed by dual-CISH), cyclin D1 (cut-off 30%) and basal cytokeratins (CK) 5/6 and 17 (cut-off 10%). Tumors were classified according to the immunophenotype as luminal (ER and or PR ≥10%, HER2-negative), HER2-positive and triple-negative (ER/PgR/HER2-negative). For PIK3CA mutation, DNA was extracted from formalin-fixed, paraffin-embedded tissues using standard methods. We analyzed by allelic discrimination based on real-time chemistry TaqMan MGB probes in ABI Prism 7500 Sequence Detection System (Applied Biosystems). Significant associations were identified using Chi-square and Fisher's exact test. A p-value <0.05 was considered significant.
Results: PIK3CA mutations were observed in 24.6% tumors. In relation with IHC variables, 76.7% tumors were positive for ER,63% for PgR, 35% for HER2, 31.3 % for p53, 6.4% for EGFR, 68.9% for cyclin D1, 13.5 % for CK 5/6 and/or CK17) and 43.1% high Ki67. Tumors with PIK3CA mutations were more frequently positive for ER (p=0.008) and PgR (p=0.003), with low Ki67 (p=0.04), and negative basal CKs (p=0.005) and luminal phenotype (p=0.036).
Conclusions: Our findings in a series of LNPBC confirm that PIK3CA mutations are associated with luminal phenotype, low proliferative activity with Ki67 and negativity for basal cytokeratins. Supported by grant FIS 06/1488
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 4, Wednesday Afternoon