mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Autor: Jina Gaber, Cecilia Svanholm-Barrie, Aureli Torné, Lorena Marimon, Marta del Pino, Amaia Sagasta, David H. Persing, Jaume Ordi
Rok vydání: 2015
Předmět:
Pathology
medicine.medical_specialty
Cytodiagnosis
Survivin
Uterine Cervical Neoplasms
Cell Cycle Proteins
Endocervical curettage
Sensitivity and Specificity
Inhibitor of Apoptosis Proteins
Pathology and Forensic Medicine
Antigens
Neoplasm
Cytology
Biomarkers
Tumor
Humans
Medicine
RNA
Messenger
Pap test
Poly-ADP-Ribose Binding Proteins
Cyclin-Dependent Kinase Inhibitor p16
Early Detection of Cancer
Vaginal Smears
Colposcopy
Cervical cancer
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Uterine Cervical Dysplasia
medicine.disease
Immunohistochemistry
DNA-Binding Proteins
DNA Topoisomerases
Type II
Matrix Metalloproteinase 9
Cytopathology
Liquid-based cytology
DNA
Viral
Biomarker (medicine)
Female
business
Zdroj: Modern Pathology. 28:312-320
ISSN: 0893-3952
DOI: 10.1038/modpathol.2014.106
Popis: Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n=28), or harboring low-grade SIL (n=47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL.
Databáze: OpenAIRE
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