Loss of heterozygosity and allelic imbalance in apocrine adenosis of the breast

Recently, there have been studies suggesting that apocrine adenosis of the breast is a putative precancerous lesion, despite the generally held view t hat apocrine adenosis is benign. Because apocrine adenosis is almost always present as a small area or areas, it cannot be easily studied by conventio nal methods. In this study, areas of apocrine adenosis were microdissected from archival paraffin-embedded tissue to examine loss of heterozygosity an d allelic imbalance compared with normal breast tissue epithelium from the same patients. Seventeen cases of apocrine adenosis, four associated with c arcinoma, were analyzed using polymorphic microsatellite markers and polyme rase chain reaction for loss of heterozygosity/allelic imbalance at eight l oci that were reported to show allele loss or imbalance in invasive and in situ breast cancer Loss of heterozygosity/allelic imbalance was detected in six of 17 cases of apocrine adenosis; three of 12 (25%) informative cases at 1p (MYCL1), two of seven (28.6%) at 11q (INT2), one of three (33.3%) at 13q (D13S267). two of 12 (16.7%) at 16q (D16S539), and two of 10 (20%) at 1 7q (D17S250). Neither loss of heterozygosity nor allelic imbalance has been identified at 1p (D1S252), 17p (TP53), or 17p (D17S513). In two of the fou r caves associated with carcinoma, loss of heterozygosity/allelic imbalance was seen in the same allele as in the synchronous carcinoma. These results suggest that molecular alterations, such as: loss of heterozygosity and al lelic imbalance, identified in apocrine adenosis may constitute an early ev ent in the pathogenesis of breast cancer; reinforcing the possibility of ap ocrine adenosis being a putative precancerous lesion.