title: CYP3A isoforms in Ewing's sarcoma tumours: an immunohistochemical study with clinical correlation.
abstract: Ewing's sarcoma is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.
authors: Department of Pathology, University of Missouri, Kansas City, MO, USA.
authors: Hamid
authors: H
authors: Zia
authors: Department of Pathology, University of Aberdeen, Aberdeen, UK.
authors: Graeme I
authors: GI
authors: Murray
authors: Department of Clinical Pharmacology, Children's Mercy Hospital, Kansas City, MO, USA.
authors: Carrie A
authors: CA
authors: Vyhlidal
authors: Department of Clinical Pharmacology, Children's Mercy Hospital, Kansas City, MO, USA.
authors: J Steven
authors: JS
authors: Leeder
authors: Department of Epidemiology and Biostatistics, College of Public Health and Health Informatics, King Saud Bin Abdulaziz University, Riyadh, Saudi Arabia.
authors: Ahmed E
authors: AE
authors: Anwar
authors: Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA.
authors: Marilyn M
authors: MM
authors: Bui
authors: Department of Pathology, Children's Mercy Hospital, Kansas City, MO, USA.
authors: Atif A
authors: AA
authors: Ahmed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D001189:Aryl Hydrocarbon Hydroxylases; C510164:CYP3A5 protein, human; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: CYP3A4; Ewing's sarcoma; Immunohistochemistry; cytochrome p450