Clonal Analysis of Peripheral Papilloma and Cancerous Cells of the Breast

摘要

Objective Because almost all malignancies represent monoclonal proliferations, we have studied the clonal status of peripheral papillomas (peri-PM), ductal carcinomas in situ (DCIS), and normal breast tissues to explore a reliable way to distinguish benign and malignant (or pre-malignant) cases previously diagnosed morphologically. METHODS Twenty-six cases of peri-PM, 25 cases of peri-PM with atypical ductal hyperplasia (ADH), 27 cases of DCIS, 16 cases of developed can-ceration and 20 specimens of normal tissue were examined in the study. The clonal status of these tissues was studied using an assay based on inacti-vation mosaicism of the lenth-polymorphic X-chromosomes at the androgen receptor (AR) locus. RESULTS Loss of polymorphism at the AR locus was found in all DCIS cases and 10 cases (10/25, 40.0%) of peri-PM with ADH, indicating the monoclonality of the tumors. Twenty-four out of 26 (92.3%) cases with peri-PM and 19 specimens of normal tissue were shown to be polyclonal. In 16 cases of developed canceration, identical X chromosome inactivation (monoclonal alterations) was observed from both the peri-PM with ADH part, and the DCIS part in each case. CONCLUSION These results contribute to the understanding of the genetic changes of peri-PM, and confirm the peri-PM with ADH as a precancer-ous lesion of the breast. Clonal analysis might be a useful modality to screen high-risk cases from precancerous lesions or to distinguish between benign hyperplasia and early carcinoma.