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Sorted By Test Name - Mayo Medical Laboratories

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EVERO<br />

60537<br />

83656<br />

Clinical References: Homburger HA: Allergic diseases. In Clinical Diagnosis and Management by<br />

Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. New York, WB Saunders<br />

Company, 2007, Chapter 53, Part VI, pp 961-971<br />

Everolimus, Blood<br />

Clinical Information: Everolimus is an immunosuppressive agent derived from sirolimus<br />

(rapamycin). Both drugs function via inhibition of mTOR signaling, and share similar pharmacokinetic<br />

and toxicity profiles. Everolimus has a shorter half-life than sirolimus, which allows for more rapid<br />

achievement of steady-state pharmacokinetics. Everolimus is extensively metabolized, primarily by<br />

CYP3A4, thus its use with inducers or inhibitors of that enzyme may require dose adjustment. The most<br />

common adverse effects include hyperlipidemia, thrombocytopenia, and nephrotoxicity. Everolimus is<br />

useful as adjuvant therapy in renal cell carcinoma and other cancers. It recently gained FDA approval for<br />

prophylaxis of graft rejection in solid organ transplant, an application which has been accepted for years<br />

in Europe. The utility of therapeutic drug monitoring has not been established for everolimus as an<br />

oncology chemotherapy; however, measuring blood drug concentrations is common practice for its use in<br />

transplant. Therapeutic targets vary depending on the transplant site and institution protocol. Guidelines<br />

for heart and kidney transplants suggest that trough (immediately prior to the next scheduled dose) blood<br />

concentrations between 3 to 8 ng/mL provide optimal outcomes.<br />

Useful For: Management of everolimus immunosuppression in solid organ transplant<br />

Interpretation: Therapeutic targets vary by transplant site and institution protocol. Heart and kidney<br />

transplant guidelines suggest a therapeutic range of 3 to 8 ng/mL. Measurement of drug concentrations in<br />

oncology chemotherapy is less common, thus no therapeutic range is established for this application.<br />

Reference Values:<br />

3-8 ng/mL<br />

Clinical References: 1. Eisen HJ, Tuzcu EM, Dorent R, et al: Everolimus for the prevention of<br />

allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003;349(9):847-858<br />

2. Kovarik JM, Beyer D, Schmouder RL: Everolimus drug interactions: application of a classification<br />

system for clinical decision making. Biopharm Drug Dispos 2006;27(9):421-426 3. Rothenburger M,<br />

Zuckermann A, Bara C, et al: Recommendations for the use of everolimus (Certican) in heart<br />

transplantation: results from the second German-Austrian Certican Consensus Conference. J Heart Lung<br />

Transplant 2007;26(4):305-311 4. Sanchez-Fructuoso AI: Everolimus: an update on the mechanism of<br />

action, pharmacokinetics and recent clinical trials. Expert Opin Drug Metab Toxicol 2008;4(6):807-819<br />

Ewing Sarcoma (EWS), 22q12 (EWSR1) Rearrangement, FISH,<br />

Tissue<br />

Clinical Information: Ewing sarcoma (EWS)/primitive neuroectodermal tumors (PNET) are<br />

members of the small, round cell group of tumors that are thought to originate in cells of primitive<br />

neuroectodermal origin with variable degrees of differentiation. The small, round cell group of tumors<br />

also includes rhabdomyosarcomas, desmoplastic small, round cell tumors, and poorly differentiated<br />

synovial sarcomas. Although immunohistochemical markers can be helpful in the correct diagnosis of<br />

these tumors, recent molecular studies have shown the specificity of molecular markers in differentiating<br />

specific subtypes of small, round blue-cell tumors. Accurate diagnosis of each tumor type is important for<br />

appropriate clinical management of patients. Ewing tumors are characterized cytogenetically by<br />

rearrangements of the EWSR1 gene at 22q12 with FLI1 at 11q24 (t[11;22]) or ERG at 21q22 (t[21;22]) in<br />

85% and 5% to 10% of Ewing tumors, respectively. Less than 1% of cases may have other fusion partners<br />

such as ETV1 at 7p22, E1AF at 17q12, or FEV at 2q33. Detection of these transcripts by reverse<br />

transcriptase-PCR (RT-PCR) (#83363 Ewingâ€s Sarcoma/Primitive Neuroectodermal Tumors<br />

[ES/PNET] by Reverse Transcriptase PCR [RT/PCR], Paraffin), which allows specific identification of<br />

the t(11;22) and the t(21;22), has greatly facilitated the diagnosis of Ewingâ€s tumors. However, if the<br />

quality of the available RNA is poor, the results are equivocal, or if a rare translocation partner is present,<br />

Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or <strong>Mayo</strong><strong>Medical</strong><strong>Laboratories</strong>.com Page 703

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