Numerous investigations have shown that in primary breast
adenocarcinomas DNA aneuploidy in contrast to
DNA diploidy indicates high
malignancy potential. On the basis of the study of 104
breast carcinomas, we describe a subtype of
aneuploidy, which demonstrates a low degree of
malignancy. In image cytometric
DNA histograms, this subtype possessed a low percentage (< or = 8.8%) of nonmodal
DNA values as measured by the stemline scatter index (SSI), which is defined as sum of the percentage of cells in the S-phase region, the G(2) exceeding rate and the coefficient of variation of the
tumor stemline. The cut point of SSI = 8.8% (P = 0.03) enabled us to also subdivide diploid and
tetraploid tumors into clinically low and high malignant variants. One possible reason for
aneuploidy is impaired distribution of chromosomes at mitosis caused by numerical or structural centrosome aberrations.
Cyclins A and E seem to be involved in centrosome duplication. Real-time quantitative PCR measurements of
cyclin A and E transcript levels and immunohistochemical determination of
cyclin A protein expression showed statistically significantly increased values in the
tumors with a high SSI (>8.8%), compared with those with a low SSI. A pilot study demonstrated centrosomal aberrations in an average of 9.6% of the measured cells in four
aneuploid carcinomas with high SSI values and in an average of 2.5% of the cells in three
aneuploid and three diploid
tumors with low SSI. Our data indicate that the SSI, most likely reflecting the degree of
genomic instability, allows additional classifying of the known
aneuploid, diploid, and
tetraploid categories of primary breast
adenocarcinomas into low and high malignant subtypes.