POLYMERASE CHAIN REACTION-BASED DETECTION OF CLONALITY AS A NON-MORPHOLOGIC DIAGNOSTIC-TOOL FOR FINE-NEEDLE ASPIRATION OF THE BREAST

BACKGROUND, Fine-needle aspiration (FNA) of breast specimens can be di fficult and between 10-25% of the lesions ultimately are classified as ''atypical,'' even by the most experienced cytopathologist. The goal of this study was to identify a molecular mechanism that reliably dist inguishes benign and malignant (or premalignant) lesions and that coul d be used as an adjunct in these morphologically ambiguous cases. METH ODS. Because all malignancies represent clonal proliferations, assessm ent of clonality represents a potential molecular mechanism for making this distinction. Excess material preserved from breast FNAs was exam ined using the human androgen receptor locus clonality assay. This ass ay allows determination of clonality on the basis of X chromosome inac tivation as detected by polymerase chain reaction analysis of genomic DNA after methylase-sensitive restriction digestion. RESULTS. In this pilot study, 25 cases showed reproducible results. All malignant cases (9 of 9) were monoclonal, whereas 10 of 12 benign cases were polyclon al. Of four atypical cases, two were monoclonal and both were found to be malignant after surgical resection. Monoclonality was observed in two benign cases that were hyperplastic lesions. CONCLUSIONS. These pr eliminary results suggest that this test may provide a non-morphologic molecular mechanism for the objective categorization of breast FNAs, Cancer (Cancer Cytopathol) 1998;84:262-7. (C) 1998 American Cancer Soc iety.