Positive margins, fibroproliferation in the surrounding breast tissue, and necrosis are associated with a marked increase in LR rates. Efforts should be made to achieve negative surgical margins to reduce risk of LR. Death from PT is rare (2%), and only PT that demonstrate uniformly aggressive pathologic features seem to be associated with mortality.

Investigators in the United

No abstract

Bone marrow examination has become increasingly important for the diagnosis and treatment of hematologic and other illnesses. Morphologic evaluation of the bone marrow aspirate and biopsy has recently been supplemented by increasingly sophisticated ancillary assays, including immunocytochemistry, cytogenetic analysis, flow cytometry, and molecular assays. With our rapidly expanding knowledge of the clinical and biologic diversity of leukemia and other hematologic neoplasms, and an increasing variety of therapeutic options, the bone marrow examination has became more critical for therapeutic monitoring and planning optimal therapy. Sensitive molecular techniques, in vitro drug sensitivity testing, and a number of other special assays are available to provide valuable data to assist these endeavors. Fortunately, improvements in bone marrow aspirate and needle technology has made the procurement of adequate specimens more reliable and efficient, while the use of conscious sedation has improved patient comfort. The procurement of bone marrow specimens was reviewed in the first part of this series. This paper specifically addresses the diagnostic interpretation of bone marrow specimens and the use of ancillary techniques.

Signal transducer and activator of transcription (Stat) 5a is a transcription factor mediating the action of specific cytokines, growth factors and hormones on gene expression. In the mammary gland, Stat5a is well recognized for its function in prolactin signaling, lobuloalveolar development, and milk protein expression during pregnancy and lactation. Latent cytoplasmic Stat5a is activated by tyrosine phosphorylation and following dimerization undergoes nuclear import. In the current study, Stat5a expression was examined immunohistochemically in carcinomas induced by the chemical carcinogens 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A high percentage of carcinomas showed nuclear labeling of Stat5a [44 of 68 (65%)] with Stat5a nuclear labeling index ranging from 18 to 77%. In contrast, control normal mammary gland tissue displayed cytosolic expression. Carcinomas with different Stat5a staining patterns (cytoplasmic or nuclear) showed a statistical difference for the proliferating cell nuclear antigen (PCNA) labeling, tumor differentiation, nuclear grade, mitotic activity, and tumor size. High Stat5a nuclear expression was closely correlated with the higher-grade carcinomas. Stat5a nuclear expression was also detected in intraductal proliferations (10 of 21 lesions) and in ductal carcinomas in situ (13 of 15 lesions). Immunohistochemical analysis was further carried out in human breast cancers. Stat5a nuclear expression was detected in ductal and lobular carcinomas and DCIS at a frequency of 48% (15/31), 33% (2/6), and 40% (2/5), respectively. Nuclear expression of Stat5a in human breast cancers also correlated with the PCNA nuclear labeling index. The findings implicate activated Stat5a in mammary gland cancer development in the rat and human.