Ki-67 and P16 proteins in cervical cancer and precancerous lesions of young women and the diagnostic value for cervical cancer and precancerous lesions.
Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific.
We aimed to investigate the expression and clinical significance of cyclin-dependent kinase inhibitor 2A (P16<sup>INK4A</sup>), sex determining region Y-box 2 (SOX2), and Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) in cervical cancer treated with radiotherapy and cervical cell line models.
The mRNA expression levels of OVCA1, cyclin D1 and p16 in cervical cancer and normal cervix cells were detected using real-time polymerase chain reaction.
By overlapping these dysregulated genes, we found that three genes, including CDKN2A, IL1R2 and RFC4, were not only changed in HSIL, but also significantly changed in SCC, indicating that their dysregulation may contribute to cervical cancer development.
The methylation of the p16 gene promoter could significantly reduce p16 expression, losing its tumor suppressor activity and promoting the development of cervical cancer.
P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively.
To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer.
Under those conditions, p16INK4a expression was always elevated during the late stage of limited cell lifespan, suggesting that cervical epithelial cells possess an intrinsic property of uniquely stringent activation of p16INK4a, which may offer an explanation for the rarity of HPV-negative cervical cancer.
Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer.
Moreover, p16 protein was associated with CIN grade and lymph node metastases in cervical cancer (all P<0.05); survivin protein was also related with clinical stages, CIN grade and lymph node metastases (all P<0.05); the p16 and survivin expressions were positively correlated with cervical cancer (r=0.854, P<0.001), and associated with poor prognosis of cervical cancer.
The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens.
1) To analyze the expression of Ki-67, p53 and p16(INK4a) in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution.
We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer.
And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P=0.0004, OR=0.04, 95% CI=0.002-0.63). p16 (540C/580T) has emerged as a major risk haplotype (P=0.033, OR=1.47, 95% CI=1.05-2.07) whereas p16 (540G/580T) as a chief protective haplotype (P=0.014, OR=0.39, 95% CI=0.18-0.83) for the development of cervical cancer among Indian women.
The knowledge about human papillomavirus as a causative agent of cervical cancer has accumulated over the last decades has opened the possibility to improve the existing prevention strategies and screening practices. p16 has amply been applied on cytologic samples and has been shown to be a promising marker especially in identification of high-grade dysplasia.