Abstract
Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05) was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q). Significant univariate correlations (p≤0.05) with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.
Highlights
Breast cancer is the most prevalent cancer among women in industrialized countries
A wide variety of chromosomal imbalances have been detected by comparative genomic hybridization (CGH) in invasive breast carcinomas
In the study presented here we have investigated a small cohort of patients with invasive breast carcinomas (15 node-negative, 24 node-positive), selected on the basis of a long-term follow-up period
Summary
Classification and prognostication are traditionally based on histopathological parameters such as tumor grade, size, and In addition to these features, quantitative cytometric measurements including the rate of proliferation, DNA histogram type, and morphometric parameters such as anisokaryosis have been shown to provide additional prognostic criteria [1,2,3,14,24]. Isola et al [18] suggested a prognostic value for DNA gains on chromosomal regions 20q and 8q in exclusively node-negative tumors that were 2 to 4 cm in size. From all tumors image cytometric data were available, which have already been proven in former studies to be of prognostic value as for example DNA histogram parameters [3,14] and variation in nuclei size (anisokaryosis) [2,3].
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