p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia

Rudiger Klaes, Axel Benner, Tibor Friedrich, Rudiger Ridder, S Herrington, David Jenkins, Robert J. Kurman, Dietmar Schmidt, Mark Stoler, Magnus von Knebel Doeberitz

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    366 Citations (Scopus)

    Abstract

    It has been repeatedly shown that there is a substantial lack of interobserver reproducibility in the histologic diagnosis of cervical intraepithelial neoplasia (CIN), which might be improved by a more specific diagnostic biomarker. Cervical cancer and CIN, but not other cervical epithelia, express high levels of the cyclin-dependent kinase inhibitor p16(INK4a), suggesting that staining for this marker could help to more precisely identify CIN in tissue sections and therefore reduce variation in interpretation of cervical lesions. To test this hypothesis, 194 cervical cone biopsy samples were selected from a routine histopathology laboratory. Two consecutive sections from each biopsy were stained with hemaoxylin and eosin and with a p16(INK4a)-specific monoclonal antibody, respectively. Five experienced cervical pathologists examined the slides. The agreement in the diagnosis between pairs or groups of observers was calculated by kappa statistics. Significant discrepancies were observed in the diagnostic interpretation of hematoxylin and eosin-stained slides, particularly for low-grade lesions (kappa value 0.60 [95% confidence interval 0.58-0.63]). There was significantly better agreement in the interpretation of p16(INK4a) expression (kappa value 0.91 [95% confidence interval 0.84-0.99]). Expression of p16(INK4a) was restricted to CIN 2/CIN 3, CIN I associated with high-risk human papillomavirus, or cervical cancer. p16(INK4a) immunostaining allowed precise identification of even small CIN or cervical cancer lesions in biopsy sections and helped to reduce interobserver variation in the histopathologic interpretation of cervical biopsy specimens. Thus, p16(INK4a) immunohistochemistry can reduce false-negative and false-positive biopsy interpretation and thereby significantly improve cervical (pre)-cancer diagnosis.

    Original languageEnglish
    Pages (from-to)1389-1399
    Number of pages11
    JournalAmerican Journal of Surgical Pathology
    Volume26
    Issue number11
    Publication statusPublished - Nov 2002

    Cite this

    Klaes, R., Benner, A., Friedrich, T., Ridder, R., Herrington, S., Jenkins, D., ... Doeberitz, M. V. K. (2002). p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. American Journal of Surgical Pathology, 26(11), 1389-1399.
    Klaes, Rudiger ; Benner, Axel ; Friedrich, Tibor ; Ridder, Rudiger ; Herrington, S ; Jenkins, David ; Kurman, Robert J. ; Schmidt, Dietmar ; Stoler, Mark ; Doeberitz, Magnus von Knebel. / p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. In: American Journal of Surgical Pathology. 2002 ; Vol. 26, No. 11. pp. 1389-1399.
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    title = "p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia",
    abstract = "It has been repeatedly shown that there is a substantial lack of interobserver reproducibility in the histologic diagnosis of cervical intraepithelial neoplasia (CIN), which might be improved by a more specific diagnostic biomarker. Cervical cancer and CIN, but not other cervical epithelia, express high levels of the cyclin-dependent kinase inhibitor p16(INK4a), suggesting that staining for this marker could help to more precisely identify CIN in tissue sections and therefore reduce variation in interpretation of cervical lesions. To test this hypothesis, 194 cervical cone biopsy samples were selected from a routine histopathology laboratory. Two consecutive sections from each biopsy were stained with hemaoxylin and eosin and with a p16(INK4a)-specific monoclonal antibody, respectively. Five experienced cervical pathologists examined the slides. The agreement in the diagnosis between pairs or groups of observers was calculated by kappa statistics. Significant discrepancies were observed in the diagnostic interpretation of hematoxylin and eosin-stained slides, particularly for low-grade lesions (kappa value 0.60 [95{\%} confidence interval 0.58-0.63]). There was significantly better agreement in the interpretation of p16(INK4a) expression (kappa value 0.91 [95{\%} confidence interval 0.84-0.99]). Expression of p16(INK4a) was restricted to CIN 2/CIN 3, CIN I associated with high-risk human papillomavirus, or cervical cancer. p16(INK4a) immunostaining allowed precise identification of even small CIN or cervical cancer lesions in biopsy sections and helped to reduce interobserver variation in the histopathologic interpretation of cervical biopsy specimens. Thus, p16(INK4a) immunohistochemistry can reduce false-negative and false-positive biopsy interpretation and thereby significantly improve cervical (pre)-cancer diagnosis.",
    author = "Rudiger Klaes and Axel Benner and Tibor Friedrich and Rudiger Ridder and S Herrington and David Jenkins and Kurman, {Robert J.} and Dietmar Schmidt and Mark Stoler and Doeberitz, {Magnus von Knebel}",
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    Klaes, R, Benner, A, Friedrich, T, Ridder, R, Herrington, S, Jenkins, D, Kurman, RJ, Schmidt, D, Stoler, M & Doeberitz, MVK 2002, 'p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia', American Journal of Surgical Pathology, vol. 26, no. 11, pp. 1389-1399.

    p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. / Klaes, Rudiger ; Benner, Axel; Friedrich, Tibor; Ridder, Rudiger ; Herrington, S ; Jenkins, David ; Kurman, Robert J.; Schmidt, Dietmar ; Stoler, Mark; Doeberitz, Magnus von Knebel.

    In: American Journal of Surgical Pathology, Vol. 26, No. 11, 11.2002, p. 1389-1399.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - p16(INK4a) immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia

    AU - Klaes, Rudiger

    AU - Benner, Axel

    AU - Friedrich, Tibor

    AU - Ridder, Rudiger

    AU - Herrington, S

    AU - Jenkins, David

    AU - Kurman, Robert J.

    AU - Schmidt, Dietmar

    AU - Stoler, Mark

    AU - Doeberitz, Magnus von Knebel

    PY - 2002/11

    Y1 - 2002/11

    N2 - It has been repeatedly shown that there is a substantial lack of interobserver reproducibility in the histologic diagnosis of cervical intraepithelial neoplasia (CIN), which might be improved by a more specific diagnostic biomarker. Cervical cancer and CIN, but not other cervical epithelia, express high levels of the cyclin-dependent kinase inhibitor p16(INK4a), suggesting that staining for this marker could help to more precisely identify CIN in tissue sections and therefore reduce variation in interpretation of cervical lesions. To test this hypothesis, 194 cervical cone biopsy samples were selected from a routine histopathology laboratory. Two consecutive sections from each biopsy were stained with hemaoxylin and eosin and with a p16(INK4a)-specific monoclonal antibody, respectively. Five experienced cervical pathologists examined the slides. The agreement in the diagnosis between pairs or groups of observers was calculated by kappa statistics. Significant discrepancies were observed in the diagnostic interpretation of hematoxylin and eosin-stained slides, particularly for low-grade lesions (kappa value 0.60 [95% confidence interval 0.58-0.63]). There was significantly better agreement in the interpretation of p16(INK4a) expression (kappa value 0.91 [95% confidence interval 0.84-0.99]). Expression of p16(INK4a) was restricted to CIN 2/CIN 3, CIN I associated with high-risk human papillomavirus, or cervical cancer. p16(INK4a) immunostaining allowed precise identification of even small CIN or cervical cancer lesions in biopsy sections and helped to reduce interobserver variation in the histopathologic interpretation of cervical biopsy specimens. Thus, p16(INK4a) immunohistochemistry can reduce false-negative and false-positive biopsy interpretation and thereby significantly improve cervical (pre)-cancer diagnosis.

    AB - It has been repeatedly shown that there is a substantial lack of interobserver reproducibility in the histologic diagnosis of cervical intraepithelial neoplasia (CIN), which might be improved by a more specific diagnostic biomarker. Cervical cancer and CIN, but not other cervical epithelia, express high levels of the cyclin-dependent kinase inhibitor p16(INK4a), suggesting that staining for this marker could help to more precisely identify CIN in tissue sections and therefore reduce variation in interpretation of cervical lesions. To test this hypothesis, 194 cervical cone biopsy samples were selected from a routine histopathology laboratory. Two consecutive sections from each biopsy were stained with hemaoxylin and eosin and with a p16(INK4a)-specific monoclonal antibody, respectively. Five experienced cervical pathologists examined the slides. The agreement in the diagnosis between pairs or groups of observers was calculated by kappa statistics. Significant discrepancies were observed in the diagnostic interpretation of hematoxylin and eosin-stained slides, particularly for low-grade lesions (kappa value 0.60 [95% confidence interval 0.58-0.63]). There was significantly better agreement in the interpretation of p16(INK4a) expression (kappa value 0.91 [95% confidence interval 0.84-0.99]). Expression of p16(INK4a) was restricted to CIN 2/CIN 3, CIN I associated with high-risk human papillomavirus, or cervical cancer. p16(INK4a) immunostaining allowed precise identification of even small CIN or cervical cancer lesions in biopsy sections and helped to reduce interobserver variation in the histopathologic interpretation of cervical biopsy specimens. Thus, p16(INK4a) immunohistochemistry can reduce false-negative and false-positive biopsy interpretation and thereby significantly improve cervical (pre)-cancer diagnosis.

    M3 - Article

    VL - 26

    SP - 1389

    EP - 1399

    JO - American Journal of Surgical Pathology

    JF - American Journal of Surgical Pathology

    SN - 0147-5185

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    ER -