Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

<p>Abstract</p> <p>Background</p> <p>Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.</p> <p>Methods</p> <p>We performed a retrospective analysis of laboratory orders and results at a national referral laboratory to gain insight into physicians' ordering practices, specifically comparing them against the ordering practices recommended by a 2002 College of American Pathologists (CAP) consensus conference on thrombophilia testing. Measurements included absolute and relative ordering volumes and positivity rates from approximately 200,000 thrombophilia tests performed from September 2005 through August 2006 at a national reference laboratory. Quality control data were used to estimate the proportion of samples that may have been affected by anticoagulant therapy. A sample of ordering laboratories was surveyed in order to assess potential measurement bias.</p> <p>Results</p> <p>Total antigen assays for protein C, protein S and antithrombin were ordered almost as frequently as functional assays for these analytes. The DNA test for factor V Leiden was ordered much more often than the corresponding functional assay. In addition, relative positivity rates coupled with elevations in prothrombin time (PT) in many of these patients suggest that these tests are often ordered in the setting of oral anticoagulant therapy.</p> <p>Conclusion</p> <p>In this real-world setting, testing for inherited thrombophilia is frequently at odds with the recommendations of the CAP consensus conference. There is a need for wider dissemination of concise thrombophilia testing guidelines.</p

“Polysomy 17” by FISH for HER2 in breast cancer is a misnomer: results of chromosome 17 analysis by array comparative genomic hybridization.

Abstract Abstract #3008 Background: The term “polysomy 17” has been widely used to refer to breast cancer cases in which fluorescence in situ hybridization (FISH) assays for HER2 were performed and found to contain &amp;gt;3 copies of the chromosome 17 centromere (probe CEP 17, D17Z1). The proportion of breast cancers that are reported to have polysomy 17 varies, but some studies report over 40% incidence. In these cases, the centromere is assumed to be representative of the entire chromosome. In this study, we analyzed chromosome 17 in breast cancers using bacterial artificial chromosome (BAC) array comparative genomic hybridization (array CGH) to assess the incidence of whole chromosome 17 polysomy.&amp;#x2028; Design: Fresh frozen tissue from 95 breast cancers was analyzed, including 84 invasive ductal carcinomas, 10 invasive lobular carcinomas, and one case with mixed ductal-lobular features. Frozen sections were reviewed to ascertain tumor content, and genomic DNA was isolated from 25-50 mg of tissue from each case. Samples were then analyzed by array CGH using an array that included whole genome coverage as well 63 probes for chromosome 17. A subset of 29 cases was also analyzed by FISH using the Vysis Pathvysion HER2 assay, which includes a chromosome 17 centromere probe and a HER2 probe.&amp;#x2028; Results: Multiple abnormalities were identified on chromosome 17, including losses and gains in both the p and q arms. Examination of the centromeric region by array CGH showed 6 cases with gains, and 10 cases with losses. Three of six cases with centromeric gains also showed HER2 amplifications. Two cases showed polysomy by FISH. Although other chromosomes in our study exhibited whole chromosome polysomy using array CGH, no cases showed complete polysomy of chromosome 17.&amp;#x2028; Conclusions: A review of the literature for chromosome 17 polysomy in breast cancer reveals that this finding almost exclusively relies on FISH analysis using chromosome 17 centromere probes. Our analysis of 95 breast cases by array CGH did not reveal any gains of whole chromosome 17. These results suggest that whole chromosome 17 polysomy is extremely uncommon in breast cancer. Those cases that are identified to have chromosome 17 polysomy by FISH are better termed “chromosome 17 centromere amplified.” Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3008.</jats:p