35. PREDICTORS OF HER2 FISH POSITIVITY IN PRIMARY BREAST CANCER DIAGNOSIS SCORED 2+ WITH IHC: RESULTS OF A SINGLE INSTITUTION ANALYSIS

Background: HER-2 positivity in breast cancer is defined as a 3+ score in immunohistochemistry (IHC) assay (defined as uniform intense membrane staining of > 30% of invasive tumor cells) or FISH amplification (ratio of HER-2 to CEP17 of > 2.2 or average HER-2 gene copy number > six signals/nucleus for those test systems without an internal control probe). In case of 2+ staining at IHC, the test is considered equivocal, and FISH is mandatory to verify the HER-2 status. Up to 15% of breast cancer are IHC 2+. Aim of this study was to identify potential predictors of FISH positivity for those cases scored IHC 2+. Methods: During 2009, a total of 200 samples were processed for FISH assay. Among them, 161 (80.5%) were primary breast diagnoses with HER2 IHC score2+. Twelve cases (7.5%) resulted not evaluable, leaving 149 cases eligible for this analysis. We have evaluated the correlation between FISH positivity and hormone receptor expression, nuclear grade and proliferation. Results: Mean age of the patients was 64 years (range 25-97). Hormone receptors status was known in 125/149 patients (84%); 107 (86%) were ER +, 92 (74%) were PgR + , 110 (88%) were either ER or PgR +. MIB-1 was available in 121 cases (81%). The mean Ki67 value was 20% (range: 2 to 80). Nuclear grade was available in 108 cases (72.5%), 50 cases were G1 or G2 (46%) and 58 were G3 (54%). FISH resulted amplified in 41 pts. (27.5%). None of the evaluated factors was significantly associated with the probability of FISH positivity: the odds ratios for FISH positivity were 1.005 for age <50 vs >50 yrs. (p= 0.704), 1.001 for proliferation (p=0.927), 1.497 for grade 3 vs. 1-2 (p=0.269), 0.96 for hormone receptor negative vs. positive (0.960). Conclusions: In this study, hormone receptor status, nuclear grade and proliferation were not significantly associated with the probability of FISH positivity. The percentage of hormone receptor positivity in this population was surprisingly high, and we are evaluating the prevalence of hormone receptor positivity in patients with HER2 IHC 0/1+ and 3+ diagnosed during the same year . The study is ongoing to include cases diagnosed between 2000-2008