Molecular markers in Paget disease of the breast.

BACKGROUND AND OBJECTIVES: Molecular markers are increasingly being analyzed in tumor specimens because of their relevance to both prognosis and choice of therapy. Paget disease of the breast is an uncommon form of breast cancer, in which molecular markers have not been well characterized. The objective of this study was to investigate the expression of c-erbB-2, p53, Ki-67, Cyclin D1, Bcl-2, estrogen receptors (ER), and progesterone receptors (PR) in mammary Paget disease. METHODS: Archival tumor tissues from 14 patients diagnosed between 1990 and 1999 with Paget disease of the breast were analyzed for these molecular markers by using an automated immunohistochemical assay. Both the intraepidermal Paget cells and the underlying carcinoma were assessed for these markers. RESULTS: The majority of Paget cells were positive for c-erbB-2 (92.9%), Cyclin D1 (100%), and Ki-67 (85.7%), but very few were positive for Bcl-2 (14.3%). p53 was overexpressed in 42.9% of the cases, and only 28.6% were positive for ER and PR. The rate of expression of these biologic markers was similar in both the Paget cells and the underlying intraductal and/or ductal carcinoma cells. CONCLUSIONS: Tumors from patients with Paget disease of the breast were positive for c-erbB-2, Cyclin D1, and Ki-67, molecular markers commonly associated with more aggressive tumor behavior and poorer survival in breast cancer patients. Few of these tumors expressed Bcl-2 or ER and PR, which are generally associated with a better prognosis. Similar expression of these markers in both Paget cells and the underlying carcinoma supports the theory that these cells are the result of an intraepidermal spread of ductal carcinoma.

Possible association of acute inflammatory exudate in chorioamnionitis and amniotic squamous metaplasia.

Reported is a case of placental chorioamnionitis in which a dramatic absence of focal inflammatory response is observed in areas of local squamous metaplasia of the amnion. The authors do not think this observation has been reported in the literature. They describe their search to find a repeat occurrence and discuss possible implications of this finding.

Tissue ferritin concentration and prognosis in carcinoma of the breast.

Seven year follow-up data were available on 36 of 40 breast carcinoma patients in whom breast tissue ferritin concentrations at the time of surgery were known. 18 patients were alive and free of recurrence or second tumor (Group 1) and 11 died with breast cancer (Group 2). Patients with lower tissue ferritin concentrations defined as less than 319 ng/mcp (nanograms of ferritin/milligram of cytosol protein) were at reduced risk: 86% of patients with low tissue ferritin concentration survived free of recurrence or second tumor vs. 40% of patients with high tissue ferritin concentration (P = 0.0056). Mean breast carcinoma tissue ferritin concentration was 295 +/- 52 ng/mcp in Group 1 and 444 +/- 55 ng/mcp in Group 2 (P = 0.036). Lymph node involvement was predictive of mortality from breast carcinoma (P = 0.0003), but did not correlate with mean tissue ferritin concentration (P = 0.082). 10/10 (100%) patients who had both low tissue ferritin concentration and absence of lymph node involvement were in Group 1. The correlation of breast tissue ferritin concentration with histopathologic dedifferentiation and with prognosis suggests tumor tissue ferritin as a marker of malignant potential.

Tissue ferritin concentration in carcinoma of the breast.

Ferritin concentration was measured in cytosol extracts of 44 mammary carcinomas and 14 benign breast tissues. A six-fold difference was observed (mean, 364.6 +/- 223.3 ng/mcp in malignant tissue versus mean, 60.2 +/- 42.1 ng/mcp in benign tissue P less than 0.001). Thirty-five malignant tissue specimens were reviewed independently by a pathologist without knowledge of their ferritin contents. Higher concentrations of ferritin were present in malignancies with greater degrees of epithelial proliferation and plemorphism suggesting the malignant epithelium as the major site of the increased ferritin. There was no correlation between desmoplastic reaction within the tumors or inflammation within or adjacent to the tumors and ferritin concentration. Ferritin in breast tissue may be important as a marker of neoplasia, a source of elevated serum ferritin, an indicator of clinical prognosis or an immunosuppressive substance.

Age-dependent pathogenicity of group B coxsackieviruses in Swiss-Webster mice: infectivity for myocardium and pancreas.

Coxsackieviruses B1-B4 were inoculated intraperitoneally into 48-hr-old, 14-day-old, and three- to five-month-old Swiss-Webster mice. Immediate death occurred only among mice less than 48 hr old, which died from fulminant encephalitis. Older mice usually survived. Myocarditis ensued in mice less than 48 hr old that were infected with coxsackieviruses B1 and B4. Several of the surviving mice developed left ventricular aneurysms, which resulted from transmural necrotizing myocarditis. In this group (coxsackieviruses B1 and B4), pathologic changes in the heart were synchronous with maximal cardiac titers of virus. Fourteen-day-old mice infected with coxsackieviruses B2 and B3 developed nontransmural necrotizing myocarditis in which maximal pathologic changes followed peak cardiac titers of virus by several days, whereas three- to five-month-old mice infected with coxsackieviruses B1, B2, B3, or B4 showed maximal susceptibility to destructive lesions in the exocrine glandular pancreas. Therefore, specific susceptibilities to infection with coxsackieviruses group B vary with age of the mouse, virus type (and strain), and organ.