Ultrastructure of a late-stage bacterial endocarditis valve vegetation

Journal of Thrombosis and Thrombolysis - Infective endocarditis (IE) remains a severe illness with high mortality rate, despite advances in antibiotic therapy and cardiac surgery. If infectious...     

Mutations in the p53 tumor suppressor gene and early onset breast cancer

Among breast cancer patients p53 gene mutation is associated with a poor prognosis. Young women with breast cancer are more likely than older women to have a poor prognosis, but whether p53 gene mutation plays a role in breast cancer in young women is not clear. This study identified 199 breast cancer patients and tested the hypothesis that p53 gene mutation was associated with early onset breast cancer. Patients with p53 gene mutations were 3-times more likely to have an early onset breast cancer (age < or = 40 years at diagnosis) than those without p53 mutations (OR = 3.05, 95% CI = 1.10-8.45). Patients with both missense and silent mutations were 7-times more likely to have a diagnosis of early onset breast cancer (OR = 7.56, 95% CI = 2.22-25.8). Patients with mutations in exon 8 of the p53 gene were 6-times more likely to be diagnosed with early onset breast cancer (OR = 6.48, 95% CI = 1.37-30.6). These findings suggest that p53 gene mutation may hasten the onset of female breast cancer.     

GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy

BACKGROUND: Cancer cell growth is an energy-related process supported by an increased glucose metabolism. The objective of this study was to investigate the association of GLUT-1 with response to chemotherapy and outcome in patients with ovarian carcinoma. METHODS: Histologic sections of formalin fixed, paraffin embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by using polyclonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled streptavidin biotin procedure. Intensity of GLUT-1 staining was compared with disease free survival (DFS), chemotherapy response, and other clinicopathologic characteristics. RESULTS: GLUT-1 cytoplasmic membrane staining was observed in 89 of 104 (85.6%) malignant tumors. Poorly differentiated tumors showed a trend to overexpress the GLUT-1 protein compared with the more differentiated counterparts (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response to chemotherapy were more frequently GLUT-1 positive than GLUT-1 negative (80% vs. 51.5%; P = 0.036). In multivariate analysis of advanced stage disease, residual tumor (P = 0.0001) and high GLUT-1 expression levels (P = 0.028) were the only independent variables that maintained a significant association with response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of Stage III-IV (International Federation of Gynecology and Obstetrics patients showing a complete clinical response, GLUT-1 overexpression was associated with a shorter DFS. The median time to progression was 30 months in GLUT-1 strongly positive cases (> 50% of cancer cells positive) versus 60 months in GLUT-1 weakly positive cases (< or = 50% of cancer cells positive; P = 0.024). CONCLUSIONS: GLUT-1 status is an independent prognostic factor of response to chemotherapy in advanced stage ovarian carcinoma. Moreover, patients overexpressing GLUT-1 show a significantly shorter DFS. These results suggest that the assessment of GLUT-1 status may provide clinically useful prognostic information in patients with ovarian carcinoma.     

Laminin receptor in lymph node negative breast carcinoma

BACKGROUND: Expression of 67 kD laminin binding protein, 67LR, is reported to be associated with invasive and metastatic phenotypes in several types of human malignancies. In mammary carcinomas, however, the biologic role of 67LR has been less clear. The authors explored the potential biologic significance of expression of 67LR in 148 patients with axillary lymph node negative breast carcinoma. METHODS: Formalin fixed, paraffin embedded histologic sections were immunohistochemically evaluated for 67LR using monoclonal antibody MLuC5. The staining results were correlated with morphologic data as well as with estrogen receptor content and p53 product accumulation. RESULTS: There were statistically significant correlations between positivity for 67LR and lower histologic grade (P = 0.003), lower nuclear grade (P = 0.002), positivity for estrogen receptor (P = 0.003), and lack of p53 abnormality (P < 0.001). Expression of 67LR had no independent effect on the disease free or overall survival of lymph node negative patients with breast carcinoma. Nevertheless, in the subgroup of 67LR positive patients, positivity for estrogen receptor was associated with significantly longer overall survival (P = 0.008). CONCLUSIONS: The data from this study suggest that tissue expression of 67LR, as detected by antibody MLuC5, is associated with better differentiated, less aggressive forms of axillary lymph node negative breast carcinoma.