Fully automated proteomic detection of cervical dysplasia.
OBJECTIVE
To evaluate the efficacy of two biomarkers, transferrin receptor (TfR) and epidermal growth factor receptor (EGFR), for the early detection of cervical dysplasia and to explore the relationship of E5, one of three viral oncogenes expressed by the human papillomavirus (HPV), to TfR and EGFR.


METHODS
Two hundred seventy-four patients were evaluated in two separate preclinical studies using EGFR and TfR in fluorescent antibody-based assays. Cervical epithelial monolayers on glass slides were immunostained and scanned using an automated microscope platform and proprietary analysis software. Sensitivity and specificity were calculated in patient cohorts for both assays.


RESULTS
Sensitivity for high grade dysplasia (HSIL) and invasive cancer in the EGFR study was 100%; specificity was 73.3%. The TfR assay, which is completely automated, demonstrated sensitivity for HSIL and invasive cancer of 96.3%, with a specificity of 81.3% in 211 patients, from five different clinical sites.


CONCLUSIONS
Both EGFR and TfR assays detected HSIL with very high accuracy (100% and 96.3%, respectively). Specificity of the TfR assay was slightly higher (81.3%) than that of the EGFR assay (73.3%). HPV E5-induced disruption of intracellular endosomal acidification and its effects upon both EGFR and TfR may provide the specific mechanistic connection between overexpression of these receptor proteins, and HPV in fection and integration. EGFR and especially TfR show great promise as biomarkers in a highly sensitive and specific, fully automated assay for the early detection of cervical dysplasia.
Keesee
Susan K
SK
Molecular Diagnostics, Inc., Chicago, Illinois 60610, USA.
Domanik
Richard
R
Patterson
Bruce
B
D001331:Automation / Q000379:methods; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D007120:Immunochemistry; D008954:Models, Biological; D015513:Oncogene Proteins / Q000819:agonists / Q000096:biosynthesis; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000145:classification / Q000175:diagnosis*; D014764:Viral Proteins
C116205:E5 protein, cottontail rabbit papillomavirus; D015513:Oncogene Proteins; D020543:Proteome; D011990:Receptors, Transferrin; D014764:Viral Proteins; D066246:ErbB Receptors