Abstract
ABSTRACT Introduction: Diagnostic reproducibility and determination of prognostic factors in cervical intraepithelial neoplasias grades 1 and 2 are still relevant problems in the daily practice of gynecological histopathology. Objective: To correlate the value of morphological reclassification and of p16 immunoexpression in cervical intraepithelial neoplasias grades 1 and 2 with clinical outcome. Materials and methods: Sixty-six patients were included (34 with cervical intraepithelial neoplasia grade 1, and 32 with grade 2); an immunohistochemical study with p16 and reclassification according to the Lower Anogenital Squamous Terminology (LAST) Consensus and by the alternative proposal of Herfs and Crum were done; unfavorable outcome was defined as a subsequent histologic diagnosis of cervical intraepithelial neoplasia grade 3 or invasive squamous cell carcinoma. Results: We observed superior performance of the alternative morphological classification (p = 0.002) to determine unfavorable outcome. We also detected superior performance of p16 in the same determination (p = 0.002). Conclusion: The use of an alternative morphological classification is promising; in the context of the use of immunohistochemical antibodies as biomarkers, p16 showed good sensitivity and negative predictive value in the determination of cases in which the outcome was unfavorable.
Highlights
Diagnostic reproducibility and determination of prognostic factors in cervical intraepithelial neoplasias grades 1 and 2 are still relevant problems in the daily practice of gynecological histopathology
We evaluated sections obtained from paraffin blocks with tissue microarrays (TMA) – previously prepared with samples from Nuprev for use in studies about biomarkers in CINs – and sections obtained from conventional paraffin blocks: using samples of TMA blocks previously constructed, 17 CIN 1 and 13 cervical intraepithelial neoplasia grade 2 (CIN 2) cases were included; using conventional paraffin blocks, 17 CIN 1 and 19 CIN 2 additional cases were included
Figure − Photomicrograph of p16 immunohistochemical staining in cervical squamous intraepithelial lesion, demonstrating minimum criteria for positivity determination according to recommendation of LAST Consensus: strong and diffuse block staining, continuous from the basal layer, nuclear, affecting at least the lower third of epithelium (100×) LAST: Lower Anogenital Squamous Terminology
Summary
Diagnostic reproducibility and determination of prognostic factors in cervical intraepithelial neoplasias grades 1 and 2 are still relevant problems in the daily practice of gynecological histopathology. Results: We observed superior performance of the alternative morphological classification (p = 0.002) to determine unfavorable outcome. Conclusion: The use of an alternative morphological classification is promising; in the context of the use of immunohistochemical antibodies as biomarkers, p16 showed good sensitivity and negative predictive value in the determination of cases in which the outcome was unfavorable. The lowest indices of diagnostic agreement are observed in the categories of cervical intraepithelial neoplasia grade 2 (CIN 2) and grade 1 (CIN 1). At a more recent NorthAmerican study, agreement of independent reviewing gynecologic pathologists with the initial diagnosis made by pathologists of the state of New Mexico was 38.2% for CIN 1 and 38% for CIN 2(4). At a study using the diagnostic categories benign, low-grade squamous intraepithelial lesion (LSIL) (CIN 1), and high-grade squamous
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