The expression of p16 (INK4a) and Ki-67 in relation to high-risk human papilloma viral load and residual disease after conization with positive margins

Song, Seung Hun; Park, H.‐M.; Eom, Dae-Woon; Lee, J.‐K.; Lee, N.‐W.; Kim, A.‐R.; Hur, Jun Young; Lee, K.‐W.; Park, Y.‐K.; Saw, Ho Suk

doi:10.1111/j.1525-1438.2007.00891.x

Cited by 8 publications

(7 citation statements)

References 43 publications

(77 reference statements)

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“…Some researchers hypothesized that the p16 overexpression may be due to the removal of p16 inhibition by pRb, which is degraded by E7 through a ubiquitin-dependent proteinase system. 22-24 Several 17,25 These findings indirectly supported the hypothesis. In the current study, p16 expression increased in patients with high-risk HPV infection.…”

Section: Discussionsupporting

confidence: 80%

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

et al. 2008

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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.

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Section: Discussionsupporting

confidence: 80%

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

et al. 2008

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“…The inactivation of pRb by E7 causes p16 overexpression because p16 is regulated by the negative feedback of pRb [22]. Previous studies reported that p16 is associated with high-risk HPV infection and that p16 expression increases in patients infected with high-risk HPV [6,23]. We also found a signifi cant association between high-risk HPV infection and p16 expression.…”

Section: Discussionsupporting

confidence: 66%

The prognostic signifi cance of p16, Ki-67, p63, and CK17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia 1

Kim

Lee

et al. 2011

Korean J Obstet Gynecol

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ObjectiveTo evaluate the prognostic signifi cance of p16, p63, and cytokeratin (CK) 17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia (CIN) 1. MethodsBiopsy tissue samples from 33 patients diagnosed with CIN 1 were stained immunohistochemically for p16, Ki-67, p63, and CK17. The staining results were correlated with the clinical course of the disease. ResultsSeventeen of 18 (94.4%) p16-negative patients experienced regression, and only 1 patient (5.6%) developed persistent disease. Fifteen of the 16 (93.8%) Ki-67-negative patients experienced regression, and 1 patient (6.3%) developed persistent disease. Negative p16 and Ki-67 expression correlated signifi cantly with disease regression (P=0.004 and P=0.017, respectively). Fourteen of 15 (93.3%) patients negative for both p16 and Ki-67 experienced regression, and 1 patient negative for both p16 and Ki-67 (6.7%) developed persistent disease. The expression levels of p63 and CK17 were not signifi cantly associated with disease regression or persistence (P=0.149 and P=0.642, respectively). Ten of the 13 (76.9%) p16-positive patients had a high-risk HPV infection. Highrisk HPV infection was signifi cantly associated with p16 expression (P=0.049). ConclusionCIN 1 with p16-or Ki-67-negative immunohistochemical staining was associated with spontaneous disease regression. The p63 and CK17 expression patterns were not related to the behavior of CIN 1.

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“…Therefore, upregulation of P16 and Ki-67 indicated infection with HR-HPV. This observation may provide a basis for the early diagnosis of cervical lesions and was consistent with a previous report (34,36).…”

Section: Discussionsupporting

confidence: 92%

Associations between the expression of SCCA, MTA1, P16, Ki‑67 and the infection of high‑risk HPV in cervical lesions

et al. 2020

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The application of detection technologies for human papillomavirus (HPV) has increased the resection rate for cervical intraepithelial neoplasia and early cervical cancer types. However, a large number of patients still present with advanced cervical cancer upon diagnosis. Therefore, to find a marker for the early diagnosis of cervical cancer, the present study investigated the expression profiles of squamous cell carcinoma antigen (SCCA), tumor metastasis related factor-1 (MTA1), the multiple tumor suppressor gene P16, and the nucleus-associated antigen Ki-67 in cervical lesions, and evaluated the association between the four proteins and the infection of high-risk (HR)-HPV in cervical lesions. The rate of SCCA expression gradually increased with the progression of cervical lesions, but the increase in SCCA expression levels from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions was not significant (P= 0.197). The positive rate of MTA1 expression gradually increased with the development of cervical lesions, but the increase from chronic cervicitis to LSIL was not significant (P=0.258). The positive rates of P16 and Ki-67 expression exhibited significant increasing trends with the progression of cervical lesions. The expression ratio of SCCA between HR-HPV infection and non-infection groups was not statistically significant (P=0.38), but the expression ratios of MTA1, P16 and Ki-67 between HR-HPV infection and non-infection groups were statistically significant (P<0.05). These results demonstrated that the expression of SCCA, MTA1, P16 and Ki-67 increased gradually with the severity of cervical lesions. In addition, there was a positive association between the expression levels of MTA1, P16 and Ki-67 and the infection of HR-HPV in cervical lesions. Therefore, SCCA, MTA1, P16 and Ki-67 may be used to enhance the diagnostic accuracy for cervical lesions.

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The expression of p16 (INK4a) and Ki-67 in relation to high-risk human papilloma viral load and residual disease after conization with positive margins

Cited by 8 publications

References 43 publications

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

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

The prognostic signifi cance of p16, Ki-67, p63, and CK17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia 1

Associations between the expression of SCCA, MTA1, P16, Ki‑67 and the infection of high‑risk HPV in cervical lesions

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