Published in Cancer Detection and Prevention 2001; 25(3):235-240.

Loss of Heterozygosity and Allelic Imbalance in Apocrine Adenosis of the Breast

Abdel-Ghani A Selim, MBBCh, PhD,a Andy Ryan, PhD,b Ghada A. El-Ayat, MBBCh, MSc,a and Clive A Wells, FRCPath,a

aDepartment of Histopathology and the bGynaecology Cancer Research Unit, St. Bartholomew's and the Royal London School of Medicine and Dentistry, St. Bartholemew's Hospital, London EC1A 7BE, United Kingdom.

Address all correspondence and reprint requests to: Abdel-Ghani A. Selim and Clive A. Wells,Department of Histopathology, St. Bartholemew's Hospital, West Smithfield, London EC1A 7BE, UK.

ABSTRACT: Recently, there have been studies suggesting that apocrine adenosis of the breast is a putative precancerous lesion, despite the generally held view that apocrine adenosis is benign. Because apocrine adenosis is almost always present as a small area or areas, it cannot be easily studied by conventional methods. In this study, areas of apocrine adenosis were microdissected from archival paraffin-embedded tissue to examine loss of heterozygosity and allelic imbalance compared with normal breast tissue epithelium from the same patients. Seventeen cases of apocrine adenosis, four associated with carcinoma, were analyzed using polymorphic microsatellite markers and polymerase chain reaction for loss of heterozygosity/allelic imbalance at eight loci 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 17q (D17S250). Neither loss of heterozygosity nor allelic imbalance has been identified at 1p (D1S252), 17p (TP53), or 17p (D17S513). In two of four cases 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 allelic imbalance, identified in apocrine adenosis may constitute an early event in the pathogenesis of breast cancer; reinforcing the possibilty of apocrine adenosis being a putative precancerous lesion.

KEY WORDS: Apocrine, breast, allele, heterozygosity, imbalance, clonal.