Pathologic Features and Immunophenotype of Estrogen Receptor-positive Breast Cancers in BRCA1 Mutation Carriers

Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER-) with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than ER- BRCA1-related cancers to be of pure invasive ductal type (P<0.001) and to be of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P<0.0001), CK14 (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1-related cancers were significantly more often of invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more frequently had a high mitotic rate (P=0.0003), and were more often CK14+ (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER- BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1-related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1-related cancers.     

Expression of cytokeratin and erbB-2 oncoprotein in Paget's disease of the nipple. An immunohistochemical study.

The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.     

Human lumbar vertebrae. Quantitative three-dimensional anatomy.

This study details the quantitative three-dimensional surface anatomy of human lumbar vertebrae based on a study of 60 vertebrae. The two lower vertebrae (L4 and L5) appeared to be transitional toward the sacral region, whereas the upper two vertebrae (L1 and L2) were transitional toward the thoracic region. Means and standard errors of the means for linear, angular, and area dimensions of vertebral bodies, spinal canal, pedicle, pars interarticularis, spinous and transverse processes were obtained for all lumbar vertebrae. This information provides a better understanding of the spine, and allows for a more precise clinical diagnosis and surgical management of spinal problems. The information is also necessary for constructing accurate mathematical models of the human spine.     

The international reference preparation of influenza virus haemagglutinin (type A)

This paper describes the international collaborative assay that led to the establishment in 1967 of the International Reference Preparation of Influenza Virus Haemagglutinin (Type A) and the studies completed during the following years on the use of the preparation for evaluating the haemagglutinin content of 46 influenza virus vaccines in terms of international units. The WHO Expert Committee on Biological Standardization (1967) defined the International Unit as 0,09361 mg of the International Reference Preparation.     

Ultrasound in the detection of testicular tumours

Ultrasonic scanning provides high resolution sectional images of the scrotal content.
The value of ultrasound in the detection of testicular tumours is discussed based on the ultrasonic findings in the normal testis as well as the findings in two patients with malignant testicular tumours.     

The effect of IV indomethacin on the gastric mucosal electrical potential difference and blood flow in anaesthetized dogs

Summary. Indomethacin inhibits prostaglandin synthesis and causes gastric mucosal damage. The correlation between the gastric mucosal function and gastric blood flow was investigated. The intragastric liquid junction corrected potential difference (PD) across the stomach wall was used to characterize the gastric mucosal function. Mucosal blood flow was determined by the radiolabeled microsphere technique. Seven dogs were anaesthetized, intragastric PD was measured continuously and blood flow determined at basal condition during sympathetic activation, and after IV indomethacin (7·5 mg/kg). PD was unchanged during the basal period and during mild sympathetic activation. After indomethacin PD was reduced significantly (-40 ± 6 mV to -20±5 mV, measured with gastric lumen negative, mean and SD, P<0·05). Mucosal blood flow decreased during sympathetic activation and a further significant reduction was seen after indomethacin. PD and flow reductions correlated (R= 0·92). As indomethacin given IV caused a parallel impairment of gastric mucosal function and blood flow, part of the indomethacin-related mucosal damaging effects might be due to the flow reduction.     

Relationship between cellular accumulation of rhodamine 123 (R123) and cytotoxicity in B16 melanoma cells

Rhodamine 123 (R123) is a mitochondria-specific prototype anticancer agent because its target is the energy-producing mechanism of the cell. The goal of this study was to investigate the relationship between intracellular R123 accumulation and cytotoxicity in a R123-sensitive cell line (RS) and a R123-resistant subline (RR) that we developed. Cytotoxicity after exposure to R123 (0-60 micrograms/ml) was assessed using the clonogenic assay. Intracellular R123 was extracted with acid-alcohol and measured by fluorimetry. The rate of R123 accumulation over 1 hr was significantly higher (P less than 0.0001) for RS cells (4.65 +/- 0.39 micrograms/min/10(6) cells) than for RR cells (1.29 +/- 0.24 micrograms/min/10(6) cells). R123 accumulation in RS cells was strongly correlated (r = 0.80; P less than 0.0001) with cytotoxicity. Treatment of RR cells with verapamil (100 microM) reversed R123 resistance. The resulting dose-survival curve was identical to the dose-response curve of RS cells treated with R123 alone. Cellular content of R123 in RR cells treated with verapamil increased to a level similar to that of RS cells and correlated with cytotoxicity. These data suggest that cytotoxicity of R123 in B16 cells results from increased cellular accumulation of R123.