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

Ciavattini,Andrea; Sopracordevole,Francesco; Di Giuseppe,Jacopo; Moriconi,Lorenzo; Lucarini,Guendalina; Mancioli,Francesca; Zizzi,Antonio; Goteri,Gaia

doi:10.3892/ol.2016.5441

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

Authors:
- Andrea Ciavattini
- Francesco Sopracordevole
- Jacopo Di Giuseppe
- Lorenzo Moriconi
- Guendalina Lucarini
- Francesca Mancioli
- Antonio Zizzi
- Gaia Goteri
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Affiliations: Gynaecologic Section, Woman's Health Sciences Department, Marche Polytechnic University, I‑60123 Ancona, Italy, Gynecologic Oncology Unit, Department of Surgical Oncology, Oncologic Referral Centre, National Cancer Institute, Aviano, I‑33081 Pordenone, Italy, Histology Section, Department of Molecular Pathology and Innovative Therapies, Marche Polytechnic University, I‑60121 Ancona, Italy, Pathological Anatomy Section, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, I‑60121 Ancona, Italy
Published online on: November 29, 2016 https://doi.org/10.3892/ol.2016.5441
Pages: 301-306

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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.

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