p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical Intraepithelial Neoplasia Progression

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Abstract

Objective

The aim of this study was to evaluate p16INK4a, cytokeratin 7 (CK7), and Ki-67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking for differences among cases that progress to high-grade squamous intraepithelial lesion, maintain LSIL, or regress.

Materials and Methods

Sixty-six LSIL biopsies were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9% LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion. Immunostaining for these markers were performed in the first biopsy. A qualitative evaluation method was used, as well as histomorphometry, using ImageJ software. Pearson χ2, Mann-Whitney, Kruskal-Wallis, and Fisher tests were used to compare the groups (P ≤ .05). A cutoff point was assessed through receiver operating characteristic curve positive cell ratio, for each marker, as progression predictors.

Results

The mean age of patients with and without progression was 33 and 27 years (P = .006), respectively. The qualitative evaluation indicated a tendency of progression, but without statistical significance. However, through histomorphometry, the receiver operating characteristic curve analysis showed cutoff points of 0.396, 0.345, and 0.026 for p16INK4a, CK7, and Ki-67 ratios, respectively, as predictors of progression (P = .003, .03, and .002, respectively). In a logistic regression analysis, p16INK4a, CK7, and Ki-67 positive cell ratio showed a significant correlation with progression (P = .036, .012, and .006, respectively).

Conclusions

p16INK4a, CK7, and Ki-67 may represent useful biomarkers that can identify LSIL lesions that need particular attention.

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