Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ.
A clinically distinct subgroup of pure ductal carcinoma in situ presents as an extensive, high-grade lesion, which nevertheless lacks invasion. We sought to evaluate differences between those ductal carcinomas in situ presenting as large versus small lesions while controlling for high-grade, to determine whether there exist phenotypic and genetic differences between the 2 groups. Fifty-two cases of pure high-grade ductal carcinomas in situ were collected retrospectively, consisting of 27 large (>40 mm) and 25 small (<15 mm) cases. The 2 groups were compared based on genomic copy number assessed by array-based comparative genomic hybridization and by phenotype determined by immunohistochemistry for estrogen receptor, progesterone receptor, Ki-67, p53, cyclin D1, p16, cyclooxygenase 2, human epidermal growth factor receptor 2, and CD68. Large lesions presented at a younger age, with lower incidence of comedonecrosis and periductal macrophage response. Larger lesions also had significantly lower estrogen receptor expression, lower cyclin D1 expression, and lower Ki-67 index. The subset of 9 large palpable tumors had significantly lower p16/cyclooxygenase 2 expression and lower Ki-67 index compared to nonpalpable tumors. Genomically, larger lesions had fewer break points, fewer amplifications, and decreased copy number gains involving chromosome 8q and chromosome 20q when compared to the small lesions. Among pure high-grade tumors, small and large groups show specific genomic and phenotypic differences. Interestingly, larger tumors showed some molecular features associated with better prognosis. A more thorough evaluation of these differences could help identify the likelihood of recurrence or progression for in situ lesions.
Hwang, ES; Lal, A; Chen, Y-Y; DeVries, S; Swain, R; Anderson, J; Roy, R; Waldman, FM
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