Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis.
BACKGROUND
Breast cancer is a genetically complex disease, which involves the accumulation of various structural and numerical chromosomal aberrations.


OBJECTIVE
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 IIalpha (topoIIalpha)) and cell survival (caspase-3, bcl-2).


METHODS
Chromogenic in situ hybridisation with pericentromeric probes was performed for molecular analysis, while oestrogen and progesterone receptors, cerbB-2, topoIIalpha, 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 topoIIalpha (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 topoIIalpha (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.
Nakopoulou
Lydia
L
Department of Pathology, Medical School, University of Athens, Athens, Greece. lnakopou@cc.uoa.gr
Panayotopoulou
Effie G
EG
Giannopoulou
Ioanna
I
Tsirmpa
Ioanna
I
Katsarou
Sophia
S
Mylona
Eleni
E
Alexandrou
Paraskevi
P
Keramopoulos
Antonios
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis