engleski

Clinicopathological significance of polysomy 17 in breast cancer

Background: Approximately 20% - 30% of breast cancers over-express the human epidermal growth factor receptor 2 (HER-2), usually as a result of high copy number of its gene (amplification) on chromosome 17q12. HER-2 protein over-expression is associated with poor prognosis in both node negative and node positive breast cancers. It has been suggested that remaining cases of HER-2 protein over-expression are consequence of increase in HER-2 gene copy number secondary to chromosome 17 polysomy. Thus aim of this study is to evaluate influence of chromosome 17 polysomy on the results of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and prognosis. Materials and methods: Tissue microarrays (TMAs) were built from the cohort of 114 archival formalin fixed paraffin embedded invasive ductal carcinoma. Immunohistochemistry was performed for HER-2 (Dako, Glostrup, Denmark) with subsequent FISH analysis of HER-2 gene and chromosome 17 status (Vysis, Downers Grove, USA). Results: HER-2 over-expression was observed in 27 (23%) cases, 21 (18%) sample had HER-2 gene amplification while polysomy 17 was observed in 24 (20.68%) samples. Polysomy 17 showed statistically significant correlation with HER-2 IHC (p=0.0081) but there was no statistically significant correlation with HER-2 gene amplification (p=0.1299). When comparing histopathological characteristics of tumors with polysomy 17 in the absence of HER-2 gene amplification to tumors with and without HER-2 amplification we did not find statistically significant difference for any tested histopathological parameter. Kaplan-Meier survival curves showed that patients with HER-2 gene amplification had statistically significant shorter overall survival (OS) comparing to tumors without HER-2 amplification. Patients with tumors having polysomy 17 in the absence of HER-2 amplification had almost similar survival curve to HER-2 amplifying tumors (p=0.04921). Conclusion: These data implicate that polysomy 17 tumors show aggressive behavior but more work is needed to differentiate weather seen observation is consequence of aneusomy or is associated with some other gene alterations (other than HER-2) positioned at chromosome 17.

Breast cancer; chromosome 17 polysomy; HER-2; prognosis

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