Assessment of the frequency of genetic alterations (LOH/MSI) in patients with intraepithelial cervical lesions with HPV infection: a pilot study
Autor: | Justyna Kiszałkiewicz, Monika Migdalska-Sęk, Karolina H. Czarnecka, Daria Domańska-Senderowska, Dorota Pastuszak-Lewandoska, Ewa Nawrot, Ewa Brzeziańska-Lasota, Agata Karowicz-Bilińska |
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Rok vydání: | 2016 |
Předmět: |
Adult
0301 basic medicine Cancer Research medicine.medical_specialty Pathology Loss of Heterozygosity Pilot Projects Cervical intraepithelial neoplasia MLH1 Gastroenterology Loss of heterozygosity Young Adult 03 medical and health sciences 0302 clinical medicine FHIT Internal medicine medicine Humans Papillomaviridae neoplasms Aged Hematology biology business.industry Papillomavirus Infections HPV infection Microsatellite instability General Medicine Middle Aged Uterine Cervical Dysplasia biology.organism_classification medicine.disease female genital diseases and pregnancy complications 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female Microsatellite Instability business Microsatellite Repeats |
Zdroj: | Medical Oncology. 33 |
ISSN: | 1559-131X 1357-0560 |
Popis: | 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. |
Databáze: | OpenAIRE |
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