p16INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection

Calil, Luciane Noal; Edelweiss, Maria Isabel Albano; Meurer, Luíse; Igansi, Cristine Nascente; Bozzetti, Mary Clarisse

doi:10.1016/j.prp.2014.03.009

Cited by 28 publications

(25 citation statements)

References 40 publications

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“…By combined testing, the sensitivity and specificity of the diagnosis of CIN lesions are both improved. The results of our study showed the expression of p16 and Ki-67 both decreased in cervical tissues of LSIL patients in 3 months after focused ultrasound treatment, which is consistent with the results of previous reported studies [23,24].…”

Section: Discussionsupporting

confidence: 93%

“…Bean confirmed [22] that the positive rate of Ki-67 expression increased gradually in cervical inflammatory disease, CIN and cervical cancer; therefore, it could be used as a potential biomarker for cervical biopsy to identify the precancerous epithelial lesions. Researchers reported [23][24][25] that there was a positive correlation and high consistency between the expression of p16 and Ki-67 in cervical tissues. Their expressions are similar in benign cervical lesions, CIN, cancer and glandular epithelial lesions; however, the expressions of p16 and Ki-67 are significantly enhanced with the increase of the grade of CIN.…”

Section: Discussionmentioning

confidence: 99%

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Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1)

Fan

Wu³

et al. 2020

International Journal of Hyperthermia

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2020) Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 ABSTRACT Objective: This study was aimed at investigating the clinical efficacy and studying the possible mechanism of FUS applications to treat cervical intraepithelial neoplasia 1 (CIN1). Methods: This was a prospective clinical study, in which 30 patients with CIN1 (28/30 of the patients were HPV positive) were enrolled and treated with FUS therapy by gynecologist. All patients were followed up for 3 months after FUS therapy. Telephone interviews, PAP smear, colposcopic examinations, cervical biopsies and HPVDNA tests were performed to assess the safety and effectiveness of FUS therapy for HPV-positive CIN1. The expression of p16, Ki-67 and Fas in the cervical tissues were examined in order to account for the possible mechanism of FUS therapy for CIN1 with HPV infection. Results: FUS therapy was tolerated well, and no severe complications were observed in any patient. After FUS treatment, twenty-five patients were cured completely, and two cases were improved with the cervical smear results reversed to normal, and three cases remained the same status as before treatment. The total effectiveness rate was 90.00% (27/30). The expression of P16 and Ki-67 in the treated cervical tissues was significantly lower than that before treatment, and the expression of Fas was found up-regulated (all p < .05). Conclusion: FUS therapy appears to be a feasible and effective treatment for patients with HPV positive CIN1. FUS therapy may help to reduce the expression of p16 and Ki-67 and enhance the expression of Fas in the treated cervical tissues to regulate cell proliferation and increase apoptosis, and thus prevent the disease from evolving into high grade lesions. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1)

Fan

Wu³

et al. 2020

International Journal of Hyperthermia

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“…We minimized this limitation in this study through the evaluation and concordance of diagnosis by two pathologists, one original interpreter of the case and one reviewer. The use of these markers complements the doubtful diagnoses, avoiding unnecessary treatments 20,21 . The presence of Ki67 in CIN I and CIN II in uterine cervix specimens is a strong independent predictive factor for graduation and disease progression, in addition to displaying an interobserver reproducibility of 100% 22 .…”

Section: Discussionmentioning

confidence: 96%

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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“…The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is commonly correlated with the clinical course of the disease. Previous studies have shown an association between Ki-67 expression and lesion severity or growth rate, and demonstrated the use of Ki-67 expression in the analysis of vulvar and vaginal lesions caused by HPV (38,39). Therefore, the determination of Ki-67 expression appears to be a relevant complementary examination in the detection and distinction of different lesion grades of the uterine cervix.…”

Section: Discussionmentioning

confidence: 99%

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

et al. 2016

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Abstract. To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining. IntroductionThe results of Pap tests performed during routine screenings at the beginning of prenatal care are abnormal in 8-12% of cases (1). Overall, the prevalence of abnormal cervical cytology in pregnancy is similar to that of age-matched, non-pregnant women (2). The incidence of cervical intraepithelial neoplasia (CIN) in pregnancy varies among different patient populations, as it does in non-pregnant women, but when age-matched, the risk of CIN is not higher than that among women who are not pregnant, ranging between 3.4 and 10.0% (3). The management of pregnant women with abnormal cytology depends on the degree of cytological abnormality, the outcome of colposcopy, and, when necessary, directed biopsy. Since, the only diagnosis that may alter management in pregnancy is invasive cancer, the management of pregnant women with abnormal cervical cytology or biopsy-proven CIN is generally more conservative compared with management of similar cytology and histology in non-pregnant women. However, management guidelines for cervical dysplasia are not well defined and are based on data collected from non-pregn...

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p16INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection

Cited by 28 publications

References 40 publications

Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1)

Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1)

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

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

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