Abstract
Background: p16INK4a, cyclin-dependent kinase inhibitor that inhibits cyclin dependent kinase 4 and 6, is a product of the INK4a gene, involved in the phosphorylation of the retinoblastoma protein (pRB). HPV E7 protein binds specifically to pRB. The inactivation of pRB leads to enhanced p16 INK4a protein levels in the affected cells. Overexpression of p16 INK4a has been proposed as a biomarker for the identification of dysplastic lesions in histologic and cytologic samples. The aim of this study was to evaluate whether p16 INK4a could be used as an additional marker in the detection of patients with cervical intraepithelial lesions at risk of progression to invasive cancer. Methods: A total of 49 Thin Prep samples with cytologic diagnoses of Low Grade and High Grade SIL, and 20 with normal cervical cells, were included in the study. The mean age of the patients was 46 years. p16 INK4a immunostaining was performed using the CINtecTM p16INK4a Cytology Kit (Dako Cytomation) according to the instructions of the manufacturer. Samples were considered positive if a brown reaction product was present in both the nucleus and the cytoplasm (predominantly in the nucleus.). Histologic diagnoses of punch biopsies from the SIL cases were available and could be compared to the cytologic findings. Results: 17 cases from the control group were negative (85%), whereas 3 presented only a few positive metaplastic cells. In 34/37 (94.2%) cases of low grade lesions immunoreactive cells were not present but 3/37(8.1%) showed focal staining. All but one cytologic sample with HGSIL showed positive p16 INK4a immunoreactivity. The intensity of p16 INK4a protein detection correlated well with the degree of abnormality. Conclusion: Our preliminary study reveals that p16 immunostaining can be applied successfully as an adjunct to cytologic diagnostic methods in order to improve diagnostic results and detect patients at risk of cervical cancer.
Highlights
INK4a gene, involved in the phosphorylation of the retinoblastoma protein
Our preliminary study reveals that p16 immunostaining can be applied successfully as an adjunct to cytologic diagnostic methods in order to improve diagnostic results and detect patients at risk of cervical cancer
The immunocytochemical detection demonstrated that 17 cases from the control group were completely negative (85%), whereas 3 presented only a few positive metaplastic cells (Table 1)
Summary
The aim of this study was to evaluate whether p16 INK4a could be used as an additional marker in the detection of patients with cervical intraepithelial. The aim of this study was to evaluate whether p16INK4a could be used as an additional marker in the detection of patients with cervical intraepithelial lesions at risk of progression to invasive cancer
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