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Morphologically Similar Epithelial and Stromal Cells in Primary Bilateral Breast Tumors Display Different Genetic Profiles: Implications for Treatment

The morphologic features of primary bilateral breast carcinoma have been well elucidated, but it is not known whether tumors at two sides share a common genetic profile and undergo the same clinical course. To address this issue, morphologically comparable epithelial and stromal cells in 18 paired primary bilateral breast tumors were microdissected and subjected to comparisons for the frequency and pattern of loss of heterozygosity (LOH) and microsatellite instability (MI), as well as the profiles of comparative genomic hybridization. Of 18 paired bilateral epithelial samples assessed with 10 DNA markers at five chromosomes, 78 altered loci were found; of these, 23 (29.5%) displayed concurrent and 55 (70.5%) showed independent LOH, MI, or both. Of 18 paired bilateral stromal samples assessed with the same markers, 70 altered loci were seen; of these, 9 (12.9%) displayed concurrent and 61 (87.1%) showed independent LOH, MI, or both. Collectively, all the markers and 30 (83.3%) of 36 paired bilateral epithelial and stromal cells displayed significantly more (P < 0.01) independent than concurrent LOH, MI, or both. In contrast, the epithelial cells of a pulmonary small cell carcinoma metastasized to both breasts displayed concurrent LOH at each of the four altered loci. Of seven selected cases for comparative genomic hybridization, six (86%) displayed chromosomal changes, but none showed an identical pattern and frequency of changes in both breasts. The significantly higher rate of independent genetic alterations in morphologically comparable cells of paired bilateral primary breast tumors supports the notion that the development and clinical course of tumors in two sides differ substantially; consequently, different interventions might be needed for the optimal management of bilateral breast tumors.