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

Objective To explore the effects of polysomy 17 on human epidermal growth factor receptor-2 (HER-2) testing and study its clinicopathologic significance. Methods 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. Results 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,unamplified 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. Conclusion 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+nonamplified cases.Tumors displaying unamplified polysomy 17 resemble more HER-2-negative than HER-2-positive counterparts. Key words: Breast neoplasms; Human epidermal growth factor receptor-2:Immunohistochemistry; Fluorescence in situ hybridization; Chromosome 17 polysomy