ORIGINAL ARTICLE

Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis

Lydia Nakopoulou¹, Effie G Panayotopoulou¹, Ioanna Giannopoulou¹, Ioanna Tsirmpa¹, Sophia Katsarou¹, Eleni Mylona¹, Paraskevi Alexandrou¹ and Antonios Keramopoulos²

¹ Department of Pathology, Medical School, University of Athens, Athens, Greece
² First Department of Gynaecology and Obstetrics, Medical School, University of Athens, "Alexandra" Hospital, Athens, Greece

Correspondence to:
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

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 II (topoII)) 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, topoII, 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 topoII (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 topoII (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.

Abbreviations: LOH, loss of heterozygosity; topoII, topoisomerase II

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