TY - JOUR
T1 - Detection of HPV-induced cervical (pre) neoplastic lesions
T2 - a tissue microarray (TMA) study
AU - Arafa, Mohammad
AU - Boniver, Jacques
AU - Delvenne, Philippe
PY - 2008/10
Y1 - 2008/10
N2 - The aim of this study was to evaluate the usefulness of a panel of biomarkers in the characterization of human papillomavirus (HPV)-induced cervical lesions. Management of these lesions depends on their histologic confirmation. Misinterpretation especially for benign mimics results in a significant diagnostic disagreement. For these reasons, a continuous effort is still needed to discover surrogate markers, which could support the final diagnosis. Archival biopsies of normal ectocervical and endocervical tissues, squamous metaplasia, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma, adenocarcinoma in situ, and adenocarcinoma were retrieved to perform a tissue microarray (TMA). A panel of markers was tested on the TMA obtained slides by in situ hybridization (HPV DNA) and immunohistochemistry (p16, involucrin, Ki-67, and HPV L1 proteins). The sensitivity to detect high-risk HPV DNA increased with lesion's severity. In situ hybridization signals suggesting integrated viral physical status predominated in CIN II/III, squamous cell carcinoma, and glandular (pre) neoplastic lesions. The p16 and Ki-67 protein expression increased from CIN I to CIN III and to infiltrative lesions. Involucrin positivity was better appreciated in well-differentiated diagnostic entities (ectocervix, mature metaplasia, and CIN I). HPV L1 antibody detected the viral capsid protein in a low proportion of CIN I and II. In conclusion, using a panel of cervical biomarkers improves the final reporting of various HPV-induced epithelial lesions. Carefully constructed TMA with single spots of 1-mm diameter are powerful tools, which have a high reliability in representing full tissue sections.
AB - The aim of this study was to evaluate the usefulness of a panel of biomarkers in the characterization of human papillomavirus (HPV)-induced cervical lesions. Management of these lesions depends on their histologic confirmation. Misinterpretation especially for benign mimics results in a significant diagnostic disagreement. For these reasons, a continuous effort is still needed to discover surrogate markers, which could support the final diagnosis. Archival biopsies of normal ectocervical and endocervical tissues, squamous metaplasia, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma, adenocarcinoma in situ, and adenocarcinoma were retrieved to perform a tissue microarray (TMA). A panel of markers was tested on the TMA obtained slides by in situ hybridization (HPV DNA) and immunohistochemistry (p16, involucrin, Ki-67, and HPV L1 proteins). The sensitivity to detect high-risk HPV DNA increased with lesion's severity. In situ hybridization signals suggesting integrated viral physical status predominated in CIN II/III, squamous cell carcinoma, and glandular (pre) neoplastic lesions. The p16 and Ki-67 protein expression increased from CIN I to CIN III and to infiltrative lesions. Involucrin positivity was better appreciated in well-differentiated diagnostic entities (ectocervix, mature metaplasia, and CIN I). HPV L1 antibody detected the viral capsid protein in a low proportion of CIN I and II. In conclusion, using a panel of cervical biomarkers improves the final reporting of various HPV-induced epithelial lesions. Carefully constructed TMA with single spots of 1-mm diameter are powerful tools, which have a high reliability in representing full tissue sections.
KW - Biomarkers, Tumor/analysis
KW - Cervical Intraepithelial Neoplasia/diagnosis
KW - Female
KW - Humans
KW - Middle Aged
KW - Papillomaviridae/pathogenicity
KW - Papillomavirus Infections/diagnosis
KW - Polymerase Chain Reaction
KW - Precancerous Conditions/diagnosis
KW - Tissue Array Analysis
KW - Uterine Cervical Neoplasms/diagnosis
UR - http://www.scopus.com/inward/record.url?scp=55949116137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55949116137&partnerID=8YFLogxK
U2 - 10.1097/PAI.0b013e318166fd42
DO - 10.1097/PAI.0b013e318166fd42
M3 - Article
C2 - 18542030
SN - 1541-2016
VL - 16
SP - 422
EP - 432
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
IS - 5
ER -