Chromosomal aberrations as detected by array comparative genomic hybridization in early low-grade intraepithelial neoplasias of the breast

Abstract

Low-grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs concomitantly with lobular intraepithelial neoplasia (LIN). We aimed to elucidate chromosomal aberrations in these early neoplastic breast lesions with the use of array comparative genomic hybridization analysis. Laser capture microdissection of 12 archival formalin-fixed, paraffin-embedded specimens harbouring foci of both DIN1a and LIN was performed. All analysed cases of DIN1a and LIN showed chromosomal gains and losses. The aberration encountered most often was loss of 16q, noted in seven DIN1a (70% of those successfully examined) and 10 LIN (91%) cases. The next most common alteration was a gain on 1q, noted in four DIN1a (40%) and seven LIN (64%) cases. The results show concurrent chromosomal aberrations of 1q gains and 16q losses in several cases with coexisting LIN and DIN1a. These aberrations are known to be common in low-grade invasive (ductal and lobular) carcinomas as well as in more advanced (conventional) types of low-grade ductal intraepithelial neoplasia (DIN) (low-grade ductal carcinoma in situ). Our results raise the possibility of similar molecular-genetic pathways in coexisting LIN and low-grade flat DIN.