Clonal Analysis In Papillomatosis And Ductal Carcinoma In Situ Of The Breast

Papillomatosis of the breast lesions are currently classified and treated as benign proliferative disorders.They may be graded as mild, moderate or severe and there may be atypia. The presence of atypia is associated with a significantly increased risk of subsequent breast carcinoma.The severe papillomatosis has been postulated as a possible precursor lesion of breast cancer. The goal of this study was to demonstrate the clonality status of papillomatosis, ductal carcinoma in situ and normal breast tissue using an assay based on inactivation mosaicism of the lenth -polymorphic X -chromosomes at the androgen receptor locus that reliably distinguishes benign and malignant (or premalignant)lesions and that could be used as an adjunct in these morphologically ambiguous cases.To investigate this question, we analyzed 20 mild-moderade, 20 severe papillomatosis lesions from the archived pathology specimens of subjects with no previous breast malignancy and 20 situ carcinoma cases .8 severe papillomatosis cases with coincident breast malignancy and 10 normal breast tissue samples were included in the study. DNA was extracted and amplified via nested-PCR with or without previous digestion by the methylation-sensitive restriction endonuclease Hha I. The products were resolved on denaturing polyacrylamide gels and visualized through silver staining.In this pilot study, 17 cases of mild-moderade papillomatosis showed reproducible results.Among them, 14 samples were suitable for the clonality test.They were polyclonal, whereas 18 of 20 malignant cases were successfully amplified ,and showed monoclonal. Of 20 severe cases, 15 were amplified , 6 of which were monoclonal.We found that a significant subset (6/15, or 40%) of these lesions demonstrated evidence of monoclonal microsatellite alterations. Of...