Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection

Abstract

Objective:The purposes of this study were to evaluate the expression of p16 INK4a (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers. Methods: We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopydirected biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV. Results: The expression of p16 (p＜0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007). Conclusion: CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.

A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

“…It is necessary to distinguish normal from CIN of any grade, and benign or lower-grade CIN, which is mostly transient dysplasia (CIN 1), from high-grade CIN. P16 is a preferable substitute indicator for Hr-HPV infection, and its expression in CIN is widely researched and reported [1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17][18]. According to previous studies [3], p16 showing diffuse strong positivity was highly sensitive to CIN 3 and CIN 2 but insensitive to CIN 1.…”

“…P16 INK4a (p16) is a kind of anti-oncogene and considered as a preferable substitute marker for Hr-HPV infection [1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17][18]. As a cyclin-dependent kinase inhibitor, p16 competes with cyclin D1 to combine with CDK4/6 and specifically suppresses the activity of CDK4, inhibiting the CDK-induced phosphorylation of pRb and arresting the cell transition from G1 phase to S phase, thereby playing a role in feedback control of mitosis.…”

Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki‐67 in epithelial cells

“…30,31 We used a cocktail of both antibodies in one staining procedure simultaneously, thus allowing to evaluate whether p16…”

MicroRNA‑10a‑5p suppresses cancer proliferation and division in human cervical cancer by targeting BDNF

“…There are 527,600 new cervical cancer cases each year and 265,700 mortalities due to cervical cancer, which is the highest mortality rate of all gynecological malignancies (1,2). Cervical cancer is more prevalent in developing countries, where >85% of cases occur (3).…”