Flow cytometric DNA analysis of specimen mammography-guided fine-needle aspirates of ductal carcinoma in situ.

Flow cytometric studies of screening mammography detected ductal carcinoma in situ (DCIS) are limited by the lack of fresh cell samples. We have performed flow cytometric DNA analyses of specimen mammography-guided fine-needle aspirates of 50 consecutive DCIS lesions detected by screening mammography. The comedo histologic subtype had an aneuploidy rate of 39% (9 of 23); noncomedo subtypes had an aneuploidy rate of 19% (5 of 27), p=ns. Noncomedo subtypes were more likely to have low (less than 2.2%) S-phase percentages, 59% (16 of 27) as compared to comedo, 9% (2 of 23), p<0.05. High and intermediate nuclear grade DCIS lesions had an insignificantly greater rate of aneuploidy, 35% (9 of 26) and 33% (4 of 12) respectively, as compared to low nuclear grade lesions, 8% (1 of 12), p=ns. Low and intermediate nuclear grade DCIS lesions had low S-phase percentage rates of 67% and 50% respectively, as compared to the high nuclear grade lesions low S-phase percentage rate, 15%, p=ns. Aneuploidy and lesser rates of low S-phase percentages were significantly associated with necrosis and apoptosis. Our data suggest that flow cytometric DNA analysis of mammographic lesion-specific, fresh cell samples obtained by fine-needle aspiration under specimen mammographic guidance can assess mammography-detected DCIS lesions when gross fresh tissue procurement is not possible.

Flow cytometric DNA analysis of invasive carcinomas detected by screening mammography: use of specimen mammography-guided fine-needle aspirates.

Clinical studies of flow cytometric DNA analysis of breast carcinoma are often limited by the lack of fresh tissue samples from smaller, nonpalpable carcinomas. In addition, most studies measuring DNA in the current literature focus on larger palpable masses that may have less relevance to the smaller, nonpalpable lesions. A prospective study of flow cytometric DNA analysis of in vitro specimen mammography-guided fine-needle aspirates (FNAs) of 103 consecutive nonpalpable invasive carcinomas detected by screening mammography was performed to determine efficacy and explore associations with mammographic and pathological features. For 62 (60%) lesions for which DNA analysis on both FNA and standard tissue incision samples was performed, there was excellent (89%) agreement for ploidy determinations (kappa=0.77) and poor agreement for S-phase percentage determinations (kappa=0.23). Specimen mammography-guided FNA analysis detected aneuploidy in 36% of lesions overall, including 34% of 41 lesions for which standard tissue procurement was not possible. Mammographic microcalcifications had a higher aneuploid rate (14 of 28 lesions, 50%) as compared with soft tissue masses (22 of 75 lesions, 29%), P < 0.01. Lobulated masses with indistinct margins had a higher aneuploid rate (5 of 6 lesions, 83%) as compared with more irregular, spiculated masses (7 of 27 lesions, 26%), P < 0.01. The aneuploidy rate was independent of specific histological diagnosis, lesion size, nuclear grade, or nodal or estrogen receptor status. Flow cytometric DNA analysis of mammographic lesion-specific, fresh, cellular FNA samples obtained under specimen mammographic guidance can assess early invasive carcinomas when gross fresh tissue procurement is not possible. This technique could be incorporated into larger clinical follow-up studies to determine the prognostic significance of flow cytometric DNA analysis for these very early breast carcinomas.

Flow cytometric DNA analyses of benign breast lesions detected by screening mammography.

There is little information regarding flow cytometric DNA analyses of benign breast lesions. This prospective study consists of mammographic and pathological correlation of DNA flow cytometric analyses of specimen mammography-guided fine-needle aspirates (FNAs) of 189 consecutive benign breast lesions and 114 FNAs of adjacent normal tissue as a control. Clinical follow-up was also performed. Aneuploidy was detected in 14 of 189 (7%) benign lesion specimen mammography-guided FNAs and in only 1 of 114 (0.9%) FNAs of adjacent normal tissue (P = 0.01). Aneuploidy was detected in two (33%) benign intramammary lymph nodes compared with four (12%) benign lesions with atypia, one benign lesion (3%) with hyperplasia, four benign lesions (10%) with adenosis, and three (4%) other benign lesions (P = 0.01). There were no significant associations between DNA content and S-phase percentage and patient age, mammographic appearance, or extent. During a median follow-up of 40 months (range, 6-84 months), 2 of 13 (15%) patients with aneuploid benign lesions developed ipsilateral breast carcinoma compared with 5 of 175 (3%) patients with diploid benign lesions (odds ratio, 6.18; 95% confidence interval, 1.08-35.56). Our data suggest that aneuploidy, which is detected in a variety of benign breast lesions, may be associated with a higher risk of development of breast carcinoma. The combined techniques of specimen mammography-guided fine-needle aspiration and flow cytometry provide a practical translational research method for the study of benign breast disease.