Effects of polysomy 17 on HER-2 gene and protein expression and its clinicopathologic significance in breast cancer

Abstract

To explore the effects of polysomy 17 on human epidermal growth factor receptor-2 (HER-2) testing and study its clinicopathologic significance. We retrospectively analyzed the HER-2 status by fluorescence in situ hybridization (FISH) and HER-2 protein expression by immunohistochemistry (IHC) in a cohort of 619 patients with invasive breast cancer. The relationship between polysomy 17 and various clinicopathologic parameters was assessed. Polysomy 17 was observed in 31.8% of cases, but more frequently in the IHC(3+) (41.9%) than in the IHC(2+)(27.7%) and IHC(1+/0) (11.1%) subgroup (P = 0.001). There was no significant correlation between the frequency of polysomy 17 and HER-2 status in each IHC subgroup (P > 0.05). Among the cases without gene amplification by FISH, 9 of 15 IHC(3+) cases showed polysomy 17. As compared with the amplified group, un-amplified polysomy 17 patients were associated with such good prognostic indicators as greater hormone receptor positivity (P < 0.001) and lower Ki-67 index (P = 0.003) with a trend towards those with neither amplification or polysomy. The frequency of polysomy 17 is partially correlated with HER-2 protein expression but not HER-2 amplification. And polysomy 17 is a major factor in strong HER-2 protein overexpression in 3+ non amplified cases. Tumors displaying un-amplified polysomy 17 resemble more HER-2-negative than HER-2-positive counterparts.