Immunostaining by

Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis. Results: The overall agreement between pervious and consensus diagnosis was 67.5% (Kappa=0.39, P<0.001). The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant Inhibitors,research,lifescience,medical (P<0.001). The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively. Conclusion: Ki67 and p16 markers are recommended as complementary tests for differentiating Inhibitors,research,lifescience,medical between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia. Key Words: CIN, Ki67 (MIB-1), p16 INK4a Introduction Almost all of the invasive cervical cancers are preceded by cervical intraepithelial neoplasia (CIN).1,2 Persistent infections with high risk human papilloma virus (hr-HPV) types lead to CIN and

invasive cancer.3 Despite well-defined criteria, the histopathologic diagnosis is subject to high rates of discrepancy among pathologists.4-6 Supplementary Inhibitors,research,lifescience,medical methods using objective biomarkers are needed to achieve more accurate Inhibitors,research,lifescience,medical diagnosis. Ki-67 is a well-known cell proliferation marker, useful for confirmation of the diagnosis in ambiguous cases and CIN grading.2,7 p16 INK4a is a specific biomarker used for identification of dysplastic cervical epithelium with tendency to invasive cervical cancer.8,9 The diagnosis of atypical immature metaplasia (AIM) has poor intra- and inter-observer reproducibility on routine hematoxylin and eosin (H&E) stained sections because of its resemblance to CIN 3.10 Ki-67 immunostaining of AIM revealed variable results, with Inhibitors,research,lifescience,medical a

wide range of reactivity and marked overlap between HPV-negative and HPV-positive cases. Ki-67 and p16 are complementary alternative biomarkers for HPV-related cervical neoplasia.7 Cytokeratin (CK) 17 is a marker for endocervical reserve stem cells which gives rise to metaplasia and expression of CK17 that decreases and disappeares as the metaplastic epithelium RepSox mouse matures. Antibody PD184352 (CI-1040) to CK17 is used to differentiate between immature squamous metaplasia (ISM) and high grade CIN (CIN3). 11 AIM may be re-classified into metaplasia and CIN3 based on p16 and CK17 immuoreactivity and mmunohistochemistry.10 Recent studies have shown that Ki67 and p16 could be used as progression markers in cervical lesions.12 The aim of this study was to evaluate and compare staining pattern for Ki67, p16 and CK17, as adjunct tests, in differentiating CIN from benign lesions to increase the diagnostic accuracy in equivocal cases.