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This Article Full Text Full Text (PDF) All Versions of this Article: jcp.2005.027839v1 jcp.2005.027839v2 59/10/1017    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Baak, J P A Articles by Skaland, I Search for Related Content PubMed PubMed Citation Articles by Baak, J P A Articles by Skaland, I Pubmed/NCBI databases Medline Plus Health Information Cervical Cancer

Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers

¹ Stovagen University Hospital and the Gade Institute, University of Bergen, Bergen, Norway; Free University, Amsterdam, The Netherlands
² Department of Pathology, Stavanger University Hospital, Stavanger, Norway
³ Department of Gynecology, Academic Medical Center Maastricht, Maastricht, The Netherlands
⁴ Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA; Department of Obstetrics and Gynecology, Duke University Medical Center

Correspondence to:
J P A Baak
Department of Pathology, Stavanger University Hospital, Armauer Hansen Road 20, N-4068 Stavanger, Norway; baja{at}sos.no
ABSTRACT
The microscopic phenotype of cervical intraepithelial neoplasia (CIN) reflects a fine balance between factors that promote or reduce CIN development. A shortcoming of the current grading system is its reliance on static morphology and microscopic haematoxylin–eosin features of the epithelium alone. In reality, CIN is a dynamic process, and the epithelium may exhibit differing results over time. Functional biomarkers p16, Ki-67, p53, retinoblastoma protein cytokeratin (CK)14 and CK13, help in the assessment of an individual CIN’s lesion’s potential for progression and regression. The aggregate information provided by these biomarkers exceeds the value of the classic grading system. Consequently, many more CINs that will either regress or progress can be accurately identified. These findings agree with known molecular interactions between HPV and the host. For accurate interpretation of a CIN, it is essential that these biomarkers be determined quantitatively and separately in the superficial, middle and deep layers of the epithelium. Such geography-specific epithelial evaluations of quantitative biomarkers emphasise the dynamic nature of a particular CIN lesion, thereby changing the art of static morphology grading into dynamic interpretation of the diseased tissue, with a strong prognostic effect.

Abbreviations: CIN, cervical intraepithelial neoplasia; CK, cytokeratin; HLA, human leucocyte antigen; HPV, human papillomavirus; hrHPV, high-risk human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; pRb, retinoblastoma protein; SI, Stratification Index; SIL, squamous intraepithelial lesion