Proteomic assessment of breast random periareolar fine-needle aspiration specimens from high risk women using SELDI-TOF-MS.

A22

The individual discriminatory accuracy of epidemiologic breast cancer risk assessment models such as the Gail model is low. Cytologic assessment of atypia in specimens obtained by breast random periareolar fine-needle aspiration (RPFNA) appears to stratify individuals with a high Gail risk into moderate and very high risk categories. The inclusion of novel biomarkers into the predictive model should further increase the accuracy of risk assessment. Surface Enhanced Laser Ionization/Desorption Time-Of-Flight Mass Spectrometry (SELDI-TOF-MS) is a method used to survey the entire range of expressed proteins in order to detect unique protein patterns in blood and tissue, and shows promise to distinguish individuals with and without cancer. We have previously established the feasibility of this technique as a tool for breast cancer risk assessment using RPFNA specimens. The goal of this study was to determine differences in protein expression by SELDI analysis between postmenopausal women at low or high risk of breast cancer as determined by cytomorphological evaluation of RPFNA specimens. Specimens were collected during routine RPFNA of 57 postmenopausal women and processed as thin preps. Based on traditional cytomorphologic evaluation and the Masood index score, RPFNA specimens were classified as normal to low (n=29; mean Masood score of 11.3) or medium to high (n=28; mean Masood score of 15.2) cytologic abnormality. Specimens were matched for age and hormone replacement therapy (HRT) status. An aliquot from each RPFNA specimen was placed in a denaturing urea solution and analyzed in duplicate by SELDI-TOF mass spectrometry over a 3-50 kDa range using Q10 (strong anion exchange), H50 (hydrophobic), and IMAC30 (metal binding) ProteinChips at both low and high laser intensities. Candidate protein masses were identified that were differentially expressed (p< 0.05) in RPFNA specimens with medium to high compared to normal to low cytologic abnormality. Future studies should focus on the verification and identification of these protein masses associated with increased cytological abnormality. Should the protein masses prove valid, the incorporate of these tissue based biomarkers may increase the accuracy of breast cancer risk assessment and the sensitivity of risk assessment at an individual level.