Analysis of genetic copy number changes in cervical disease progression

• Published in: BMC cancer 2010-08, Vol.10 (1), p.432-432, Article 432
• Main Authors: Policht, Frank A, Song, Minghao, Sitailo, Svetlana, O'Hare, Anna, Ashfaq, Raheela, Muller, Carolyn Y, Morrison, Larry E, King, Walter, Sokolova, Irina A
• Format: Article
• Language: English
• Subjects: Analysis; Cervical cancer; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - pathology; Cervix Uteri - pathology; Chromosome Aberrations; Chromosomes; Chromosomes, Human, Pair 3 - genetics; Chromosomes, Human, Pair 8 - genetics; Development and progression; Disease Progression; DNA Copy Number Variations - genetics; Female; Gene amplification; Genetic aspects; Genetic variation; Health sciences; Human papillomavirus; Humans; In situ hybridization; In Situ Hybridization, Fluorescence; Prognosis; Uterine Cervical Dysplasia - genetics; Uterine Cervical Dysplasia - pathology; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Womens health
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-432

Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization. The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity. The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells. The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.