Gains of chromosomes 7, 17, 12, 16, and 20 and loss of Y occur early in the evolution of papillary renal cell neoplasia: a fluorescent in situ hybridization study.

It has been suggested that gains of chromosomes 7 and 17 and loss of Y occur in renal papillary adenoma and that progression to papillary renal cell carcinoma is marked by gains of additional chromosomes, most frequently 12, 16, and 20. Previous studies have included very few lesions of <5 mm in diameter, a requirement of the present definition of papillary adenoma. Ten papillary adenomas (ranging from 1 to 5 mm in diameter) from autopsy material and 10 surgically resected papillary renal cell carcinomas were studied with fluorescence in situ hybridization in paraffin sections using centromeric probes for chromosomes 7, 12, 16, 17, 20, and Y diluted 1:100 with tDenHyb1 buffer. The signals in 50 to 150 nuclei were counted in each tumor. Controls for all the probes were normal renal tissues from the same patients. Three or more signals per nucleus were frequently observed in papillary adenomas: chromosome 7 (range, 10 to 50%; > or = 30% in 9 of 10), 17 (range, 10 to 47%; > or = 30% in 7), 16 (range, 1 to 63%; > or = 10% in 5), 12 (range, 0 to 32%; > or =10% in 4), and 20 (range, 5 to 49%; > or = 10% in 5). Loss of the Y chromosome was observed in 80 to 90% of nuclei in 9 adenomas from males. Three or more signals were frequent in papillary renal cell carcinomas: chromosome 7 (range, 32 to 63%; > or =30% in 10 of 10), 17 (range, 28 to 61%; > or = 30% in 7), 16 (range, 0 to 45%; > or = 10% in 6), 12 (range, 1 to 37, > or = 10% in 5), 20 (range, 2 to 44%; > or = 10% in 4). No signal for Y was observed in 12 to 88% (> or = 81% in 6) of nuclei in 7 carcinomas from males. Statistical analysis showed no difference between adenomas and carcinomas. Gains of chromosomes 7, 17, 16, 12, and 20 and loss of the Y chromosome occur early in the evolution of papillary renal cell neoplasia in tumors that are only a few millimeters in diameter. Progressive gains of these chromosomes do not appear to correlate with the transition from adenoma to carcinoma.     

Survey of medicinal plants used as antimalarials in the Amazon.

Plants traditionally employed for the treatment of malaria in certain areas of Brazil, where this disease is prevalent, were surveyed by interviewing natives and migrants in the Amazon Region. Forty-one plants used for malarial treatment and/or for the related symptoms (fever and liver disorders) were collected and identified. Given the potential of Brazil's forests and medicinal plants, research on traditional plant-based remedies in this country may lead to the development of new drugs.     

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Quantitation in gated perfusion SPECT imaging: The Cedars-Sinai approach

Cedars-Sinai’s approach to the automation of gated perfusion single photon emission computed tomography (SPECT) imaging is based on the identification of key procedural steps (processing, quantitation, reporting), each of which is then implemented, in completely automated fashion, by use of mathematic algorithms and logical rules combined into expert systems. Our current suite of software applications has been designed to be platform- and operating system-independent, and every algorithm is based on the same 3-dimensional sampling scheme for the myocardium. The widespread acceptance of quantitative software by the nuclear cardiology community (QGS alone is used at over 20,000 locations) has provided the opportunity for extensive validation of quantitative measurements of myocardial perfusion and function, in our opinion, helping to make nuclear cardiology the most accurate and reproducible modality available for the assessment of the human heart.     

Functioning human insulinomas

Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.