Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk.

To evaluate the feasibility of nipple aspiration and to identify intermediate markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177 subjects using a modified breast pump. The first 33 subjects demonstrated that we could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining 144 subjects were collected to evaluate promising cellular biomarkers. NAF was obtained in 167 out of 177 (94%) subjects overall and in 99% of the 144 most recent subjects. Sufficient NAF was obtained to evaluate cytology in 160 out of 167 (96%) cases and specimens were sufficiently cellular to analyse DNA markers in 53% of cases. Among the last 144 subjects, menopausal status did not influence the ability to obtain NAF. NAF cytology correlated with increased breast cancer risk (P = 0.002). Using computerized image analysis of NAF epithelial cells, DNA index (P = 0.0002), percentage of cells in G2M (P = 0.05) and percentage of cells with hypertetraploidy (P = 0.002) increased as cytology became more abnormal. Our data indicate that NAF can be obtained in essentially all eligible subjects; that breast epithelial cells are evaluable in > 95% of NAF samples for cytology and in over half of NAF samples for DNA index (ploidy) and cell cycle analysis; and that abnormal NAF cytology correlates with increased breast cancer risk. This suggests that biomarkers identified in nipple aspirate fluid may prove useful either as an adjunct to currently accepted breast cancer screening methods, or to evaluate response to a chemopreventive agent.

Immunohistochemical analysis of p53 expression in human pancreatic carcinomas.

Alterations in the p53 tumor suppressor gene are involved in the pathogenesis of diverse human cancers. Immunohistochemical detection of the p53 protein has been strongly correlated with mutations in the p53 gene. Fifty-four human exocrine pancreatic tumors of American, Japanese, and Senegalese origin and six xenotransplanted human pancreatic carcinoma cell lines were investigated immunohistochemically with monoclonal anti-p53 antibodies pAb 1801 and BP53-12. Positive nuclear p53 immunoreactivity was detected in 37% of paraffin-embedded primary tumors (21.8% in the Japanese group, 52.6% in the American group) and in 50% of xenotransplanted carcinoma cell lines. Since several intraductal papillary adenocarcinomas exhibited positive p53 immunostain, it seems probable that alterations in this tumor suppressor gene occur relatively early in the process of pancreatic carcinogenesis. No clear correlation was established between p53-positive immunohistochemical staining and tumor stage and histologic appearance, nor with patient age, sex, or survival time. In contrast to ductal carcinomas and intraductal papillary adenocarcinomas, none of the mucinous or adenosquamous pancreatic carcinomas exhibited positive nuclear staining for p53. The fact that more than half of the ethanol-fixed fine-needle aspirates were positive for p53 suggests that this type of immunostain may be of potential diagnostic significance. An investigation of a large series of pancreatic tumors is needed to further evaluate the relationship between p53 alterations and clinicopathologic features in human pancreatic cancer.