The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

Fonseca, Fernanda Villar; Tomasich, Flávio Daniel Saavedra; Jung, Juliana Elizabeth; Maestri, Carlos Afonso; Carvalho, Newton Sérgio de

doi:10.1590/0100-69912016001008

Cited by 12 publications

(28 citation statements)

References 31 publications

(46 reference statements)

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“…The study by Cardoso et al 4 was one of the few that showed statistical significance between p16 ink4a overexpression and disease recurrence, as did Nam et al 25 . Fonseca et al 26 demonstrated that p16 ink4a was overexpressed in 43% of the recurrences, with high intensity in 58% of them, though this finding was not statistically significant. In a group of 90 patients with cervical intraepithelial neoplasia with overexpressed p16 ink4a and Ki67, there was progression in 15 cases (17%), two cases in the group of 25 patients with CIN I (8%) and 13 cases in the group of 65 patients with CIN II (20%) 22 .…”

Section: Discussionmentioning

confidence: 92%

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

Goulart

Gonçalves

Da-Silva

2017

Rev. Col. Bras. Cir.

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Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. Results : the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. Conclusion : there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated.

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Section: Discussionmentioning

confidence: 92%

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

Goulart

Gonçalves

Da-Silva

2017

Rev. Col. Bras. Cir.

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“…In 43% of the recurrence group and 57% of the control group, p16 was present, with a sensitivity of 66%, a specificity of 49%, a positive predictive value of 42%, a negative predictive value of 72%, and accuracy of 56%. Thus, these results showed that p16 did not predict the recurrence of HSIL after treatment [25].…”

Section: Discussionmentioning

confidence: 99%

“…Fonseca et al [25] evaluated the predictive value of p16. They assessed 83 patients with HSIL, aged between 16 and 86 years, from 1999 to 2006.…”

Section: Color Version Available Onlinementioning

confidence: 99%

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions

Arredondo-Gálvez

Acuña-González

Cantú-de-León

et al. 2021

Gynecol Obstet Invest

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Objective: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). Design: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. Methods: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher’s exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. Results: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). Limitations: Our main limitation was a reduced sample size. Conclusion: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

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“…All skin samples were sent for routine pathological staining analyses. The paraffin-embedded and formalin-fixed skin were stained for immunohistochemistry using normal hematoxilin-eosin (H&E) staining; p53 expression with monoclonal mouse Anti-human P53 protein, clone DO-7 (as described in (Fonseca et al 2016)); p63 expression with mouse monoclonal, clone DAK-p63, core DNA-binding domain of human p63 protein reacting with TAp63 and ΔNp63 isoforms of p63); cKit/CD117 expression with rabbit polyclonal.…”

Section: Gene Expression Biomarkersmentioning

confidence: 99%

Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S)

et al. 2018

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Road construction workers are simultaneously exposed to two carcinogens; solar ultraviolet (UV-S) radiation and polycyclic aromatic hydrocarbons (PAHs) in bitumen emissions. The combined exposure may lead to photogenotoxicity and enhanced PAH skin permeation rates. Skin permeation rates (J) for selected PAHs in a mixture (PAH-mix) or in bitumen fume condensate (BFC) with and without UV-S co-exposures were measured with in vitro flow-through diffusion cells mounted with human viable skin and results compared. Possible biomarkers were explored. Js were greater with UV-S for naphthalene, anthracene, and pyrene in BFC (0.08-0.1 ng/cm/h) compared to without (0.02-0.26 ng/cm/h). This was true for anthracene, pyrene, and chrysene in the PAH-mix. Naphthalene and benzo(a)pyrene (BaP) in the PAH-mix had greater Js without (0.97-13.01 ng/cm/h) compared to with UV-S (0.40-6.35 ng/cm/h). Time until permeation (T) in the PAH-mix were generally shorter compared to the BFC, and they ranged from 1 to 13 h. The vehicle matrix could potentially be the reason for this discrepancy as BFC contains additional not identified substances. Qualitative interpretation of p53 suggested a dose-response with UV-S, and somewhat with the co-exposures. MMP1, p65 and cKIT were not exploitable. Although not statistically different, PAHs permeate human viable skin faster with simultaneous exposures to UV.

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The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

Abstract: immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.

Cited by 12 publications

References 31 publications

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions

Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S)

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