title: Assessment of the frequency of genetic alterations (LOH/MSI) in patients with intraepithelial cervical lesions with HPV infection: a pilot study.
abstract: In the present study, we analyzed (1) the type of HPV infection and (2) the frequency of loss of heterozygosity and microsatellite imbalance (LOH/MSI) in normal cytology and cervical intraepithelial neoplasia (CIN1-3). The cytological material included: low-grade squamous intraepithelial lesions (CIN1, n = 11), high-grade lesions (CIN2 and CIN3, n = 13), and cytologically normal cells from non-neoplastic cervical samples (n = 8). HPV genotyping was done using RealLine HPV 16/18 kit. We used 20 microsatellite markers from: 1p31.2, 3p14.3, 3p21.3, 3p22.2, 3p24.2, 3p25.3, 7q32.2, 9p21.3, 11p15.5, 12q23.2, and 16q22.1. LOH/MSI was correlated with clinicopathological parameters. The presence of HPV DNA was revealed in 78.13 % samples, including normal cytology. LOH/MSI was the most frequent for: 3p25.3 (39 %), 3p22.2 (20.83 %), 3p24.2 (20 %), and 3p14.3 (16.67 %). It was demonstrated that D3S1234 (FHIT; 3p14.3), D3S1611 (MLH1; 3p22.2), D3S1583 (RARB; 3p24.2), D3S1317 and D3S3611 (VHL; 3p25.3) could differentiate patients with CIN2/CIN3 versus CIN1, showing significantly higher frequency in CIN2/CIN3. LOH/MSI frequency for other than 3p markers was lower, 10-22.2 %. The simultaneous occurrence of LOH/MSI for several markers (OFAL) was higher in CIN2/CIN3. Significant differences in OFAL were found between samples with versus without HPV infection. In HPV-positive patients, significant differences in OFAL were found between normal cytology, CIN1 and CIN2/CIN3. HPV infection influences the increase in LOH/MSI frequency, especially in tumor suppressor gene loci. Several studied microsatellite markers seem to be useful for CIN grading. Hopefully, the obtained results, if confirmed on larger patient cohort, would allow creating a panel of markers supporting clinical diagnosis in patients with HPV infection.
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland. monika.migdalska-sek@umed.lodz.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.affiliation: Department of Pregnancy Pathology, 1st Chair of Gynecology and Obstetrics, Medical University of Lodz, Wileńska 37, 94-029, Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Karowicz-Bilińska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Karolina H
authors.initials: KH
authors.lastname: Czarnecka
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Domańska-Senderowska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kiszałkiewicz
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Pomorska St. No. 251, 92-213, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzeziańska-Lasota
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology; D010865:Pilot Projects; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology*
keywords: Cervical intraepithelial neoplasia (CIN); HPV16/18; Loss of heterozygosity/microsatellite imbalance (LOH/MSI); Overall frequency of allelic loss (OFAL); Panel of markers