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Title: P16INK4a immunohistochemistry improves the reproducibility of the histological diagnosis of cervical intraepithelial neoplasia in cone biopsies
Author: Gurrola-Diaz, C.M.
Suarez-Rincon, A.E.
Vazquez-Camacho, G.
Buonocunto-Vazquez, G.
Rosales-Quintana, S.
Wentzensen, N.
von Knebel Doeberitz, M.
Issue Date: 2008
Abstract: Objective: Cervical cancer is currently the most frequently occurring cancer among women in Mexico. Mexican cervical cancer prevention programs have been unsatisfactory in part because the tests used to diagnose precursor lesions have poor reproducibility. The implementation ofspecific biomarkers may overcome these limitations. Here, we analyzed whether immunohistochemistry for p16INK4a could improve the reproducibility of histopathological diagnoses of cervical precancerous lesions. Methods: Serial sections of 78 specimens were stained for H&E and p16INK4a and independently interpreted by three Mexican pathologists. Specimens were interpreted and categorized in two ways: 1) four diagnostic categories including negative lesions, CIN1, CIN2, and CIN3, or 2) two diagnostic categories; either lesions that do not require therapy (negative, CIN1), or lesions that require therapy (≥ CIN2). The agreement in diagnoses between pairs of observers was evaluated by kappa statistics. Results: The best concordance in diagnosing was observed with two categories and p16INK4a staining. Interestingly, the overall diagnostic discordances of higher than one CIN grade were 26.1% for H&E and 9.20% for p16INK4a (P < 0.001). Using four diagnostic categories, weighted kappa values for each pair of observers were 0.28, 0.15, and 0.36 for H&E and 0.34, 0.35, and 0.60 for p16INK4a stains. Using two diagnostic categories, kappa values were 0.36, 0.12, and 0.18 for H&E and 0.59, 0.70, and 0.59, p16INK4a stains. Conclusion: These data show that p16INK4a immunohistochemistry substantially improved the reproducibility of interpreting histological slides. This approach may result in more accurate diagnoses and improved clinical management of patients with cervical precancerous lesions in Mexico and elsewhere. © 2008 Elsevier Inc. All rights reserved.
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