Gurrola-Díaz Carmen M, Suárez-Rincón Angel E, Vázquez-Camacho Gonzalo, Buonocunto-Vázquez Giuseppe, Rosales-Quintana Sergio, Wentzensen Nicolas, von Knebel Doeberitz Magnus
Departamento de Biología Molecular y Genómica, Instituto de Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Gynecol Oncol. 2008 Oct;111(1):120-4. doi: 10.1016/j.ygyno.2008.06.032. Epub 2008 Aug 9.
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 of specific biomarkers may overcome these limitations. Here, we analyzed whether immunohistochemistry for p16(INK4a) could improve the reproducibility of histopathological diagnoses of cervical precancerous lesions.
Serial sections of 78 specimens were stained for H&E and p16(INK4a) 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 (>or=CIN2). The agreement in diagnoses between pairs of observers was evaluated by kappa statistics.
The best concordance in diagnosing was observed with two categories and p16(INK4a) staining. Interestingly, the overall diagnostic discordances of higher than one CIN grade were 26.1% for H&E and 9.20% for p16(INK4a) (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 p16(INK4a) 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, p16(INK4a) stains.
These data show that p16(INK4a) 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.
宫颈癌是目前墨西哥女性中最常见的癌症。墨西哥的宫颈癌预防项目并不理想，部分原因是用于诊断前驱病变的检测方法重复性较差。特定生物标志物的应用可能会克服这些局限性。在此，我们分析了p16（INK4a）免疫组化是否能提高宫颈前病变组织病理学诊断的重复性。
对78个标本的连续切片进行苏木精-伊红（H&E）和p16（INK4a）染色，并由三位墨西哥病理学家独立解读。标本以两种方式进行解读和分类：1）四个诊断类别，包括阴性病变、CIN1、CIN2和CIN3；或2）两个诊断类别，即不需要治疗的病变（阴性、CIN1）或需要治疗的病变（≥CIN2）。通过kappa统计评估观察者之间诊断的一致性。
在两类诊断及p16（INK4a）染色中观察到最佳的诊断一致性。有趣的是，H&E染色高于一个CIN级别的总体诊断不一致率为26.1%，而p16（INK4a）染色为9.20%（P<0.001）。采用四个诊断类别时，H&E染色的每对观察者的加权kappa值分别为0.28、0.15和0.36，p16（INK4a）染色的分别为0.34、0.35和0.60。采用两个诊断类别时，H&E染色的kappa值分别为0.36、0.12和0.18，p16（INK4a）染色的分别为0.59、0.70和0.59。
这些数据表明，p16（INK4a）免疫组化显著提高了解读组织切片的重复性。这种方法可能会使墨西哥及其他地区宫颈前病变患者的诊断更准确，并改善临床管理。
