title: Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression.
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.
authors.affiliation: Gynaecologic Section, Woman's Health Sciences Department, Marche Polytechnic University, I-60123 Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciavattini
authors.affiliation: Gynecologic Oncology Unit, Department of Surgical Oncology, Oncologic Referral Centre, National Cancer Institute, Aviano, I-33081 Pordenone, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sopracordevole
authors.affiliation: Gynaecologic Section, Woman's Health Sciences Department, Marche Polytechnic University, I-60123 Ancona, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Di Giuseppe
authors.affiliation: Gynaecologic Section, Woman's Health Sciences Department, Marche Polytechnic University, I-60123 Ancona, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moriconi
authors.affiliation: Histology Section, Department of Molecular Pathology and Innovative Therapies, Marche Polytechnic University, I-60121 Ancona, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.affiliation: Gynaecologic Section, Woman's Health Sciences Department, Marche Polytechnic University, I-60123 Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancioli
authors.affiliation: Pathological Anatomy Section, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, I-60121 Ancona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.affiliation: Pathological Anatomy Section, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, I-60121 Ancona, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Goteri
keywords: Ki-67 antigen; cervical intraepithelial neoplasia; human papilloma virus; p16; pregnancy