Assessment of the association between the frequency of micronucleus and p16INK4a/Ki-67 co-expression in patients with cervical intraepithelial lesions.

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 p16INK4a and Ki-67 (p16INK4a/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 p16INK4a/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16INK4a/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16INK4a/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 p16INK4a/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16INK4a/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.

Relationship of homocysteine levels with lumbar spine and femur neck BMD in postmenopausal women.

OBJECTIVE: The focus of several studies in recent years has been the association between increased plasma concentrations of homocysteine (Hcy), reduced bone mineral density and increased risk of bone fractures. Nevertheless, inconsistencies persist in the literature. Thus, the objective of this study was to investigate the possible relationship between serum Hcy and vitamin B12 status, and bone mineral density, on a group of post-menopausal women. MATERIALS AND METHODS: One hundred thirty-nine postmenopausal women were recruited to enter this cross-sectional study. Bone mineral density (BMD) of total hip, femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (DXA) and serum Hcy, vitamin B12, parathyroid hormone (PTH), total calcium and magnesium levels were determined. In addition, we investigated the relationship of Hcy and vitamin B12 and BMD using a meta-analysis approach. RESULTS: Serum Hcy levels were significantly higher in osteoporotic women when compared to other BMD groups, and were inversely related to lumbar spine BMD and femur neck BMD. Body mass index and serum Hcy levels were shown to be significant predictors of BMD at lumbar spine, femur neck and total hip. The performed meta-analysis showed that serum Hcy levels were significantly higher in osteoporotic subjects compared to normal BMD subjects. CONCLUSION: This study shows that Hcy status, but not vitamin B12 status, is associated with BMD in this cohort of postmenopausal women. We therefore confirm that high Hcy levels are an independent risk factor for osteoporosis. BMD evaluation in women at post menopause with high Hcy levels may be helpful in advising precautionary measures.