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Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis
  1. Lydia Nakopoulou1,
  2. Effie G Panayotopoulou1,
  3. Ioanna Giannopoulou1,
  4. Ioanna Tsirmpa1,
  5. Sophia Katsarou1,
  6. Eleni Mylona1,
  7. Paraskevi Alexandrou1,
  8. Antonios Keramopoulos2
  1. 1Department of Pathology, Medical School, University of Athens, Athens, Greece
  2. 2First Department of Gynaecology and Obstetrics, Medical School, University of Athens, “Alexandra” Hospital, Athens, Greece
  1. Correspondence to:
 Professor L Nakopoulou
 Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias street, Goudi, GR-11527 Athens, Greece; lnakopou{at}cc.uoa.gr

Abstract

Background: Breast cancer is a genetically complex disease, which involves the accumulation of various structural and numerical chromosomal aberrations.

Aim: To assess the numerical status of chromosomes 16 and X by interphase cytogenetics, in 114 women with primary invasive breast carcinomas, in relation to clinicopathological parameters, patients’ overall survival and indices of cell growth (c-erbB-2, topoisomerase IIα (topoIIα)) and cell survival (caspase-3, bcl-2).

Experimental design: Chromogenic in situ hybridisation with pericentromeric probes was performed for molecular analysis, while oestrogen and progesterone receptors, cerbB-2, topoIIα, caspase-3 and bcl-2 expression was immunohistochemically detected (ABC/HRP). The results were statistically assessed by univariate and multivariate analyses.

Results: Polysomy of chromosomes 16 and X was detected as the predominant aberration (73.7% and 57.9%, respectively). Gain of chromosome 16 copies was associated with high nuclear grade (p = 0.009), increased tumour size (p = 0.041), advanced stage (p = 0.002), the expression of topoIIα (p = 0.005) and worse overall survival by multivariate analysis (p = 0.032). Chromosome X polysomy was increased in ductal carcinomas of high histological grade (p = 0.008), in high nuclear grade tumours (p = 0.001), and was associated with the expression of topoIIα (p = 0.005), loss of caspase-3 (p = 0.036) and impaired prognosis of ductal carcinomas (p = 0.041).

Conclusions: Polysomy of chromosomes 16 and X was reported as the predominant alteration in phenotypically aggressive breast tumours, characterised by poor differentiation, increased growth potential and impaired prognosis, whereas gain of chromosome X in particular is probably implicated in cell survival.

  • LOH, loss of heterozygosity
  • topoIIα, topoisomerase IIα

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Footnotes

  • Competing interests: None declared.

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