Assessment of the association between the frequency of micronucleus and p^16INK4a/Ki-67 co-expression in patients with cervical intraepithelial lesions

Abstract

Human papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16 and Ki-67 (p16/Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes. We analyzed the association between the frequency of MN in PBL and the amount of p16/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16/Ki-67 co-expression restricted to the lower part of the epithelium and were considered low positive and the remaining 60% of cases were negative. The frequency of MN, NPBs and NBUDs differed significantly among groups. We found a statistically significant positive correlation between p16/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16/Ki-67 double immunostaining for histological samples with CIN 1. MN frequency in PBL might be useful for detecting genomic instability in cases of HPV infection and CIN.

Predict the Progression of Cervical Intraepithelial Neoplasia by a Novel Marker Folate Combine with FRα, p16 and Ki-67

“…The overexpression of p16 has been observed in most cervical cancers and cancers. 17 This study verified that there were significant differences in p16 staining between the CIN group of each grade and the normal control group, that the positive expression rate increased with increasing disease grade, and that there was a positive correlation with disease grade. However, univariate logistic analysis did not verify that p16 is an independent risk factor for CIN progression, which is inconsistent with the conclusions of other studies.…”

Predict the Progression of Cervical Intraepithelial Neoplasia by a Novel Marker Folate Combine with FRα, p16 and Ki-67

“…Therefore, p16 is considered a surrogate marker for persistent high-risk HPV infection. The overexpression of p16 has been observed in most cervical cancers and cancers [12]. This study veri ed that there were signi cant differences in p16 staining between the CIN group of each grade and the normal control group, that the positive expression rate increased with increasing disease grade, and that there was a positive correlation with disease grade.…”