Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia

Kurtycz, Daniel F.I.; Nuñez, M.; Arts, T.; Bauman, C.; Harris, Chad; Inhorn, Stanley L.; Meisner, Lorraine F.

doi:10.1002/(sici)1097-0339(199607)15:1<46::aid-dc9>3.0.co;2-o

Cited by 25 publications

(6 citation statements)

References 11 publications

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“…18 -23 In 98% of squamous cell carcinomas of the uterine cervix, DNA aneuploidy as the cytometric equivalent of cytogenetic aneuploidy can be detected, 16,24,25 but so far it has not been found in normal or in reactive squamous cells of the cervix. 20,26,27 Precancerous lesions of the uterine cervix show cytogenetic aneuploidy 28 as a marker of transition into aneuploid carcinomas. 29 -31 This aneuploidy has been demonstrated with cytometric methods as well.…”

Section: Discussionmentioning

confidence: 99%

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

Bollmann¹,

Bollmann²,

Henson³

et al. 2001

Cancer

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Section: Discussionmentioning

confidence: 99%

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

Bollmann¹,

Bollmann²,

Henson³

et al. 2001

Cancer

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“…9 Deletion, duplication, and amplification of various genomic regions have been demonstrated in cervical cancer by comparative genomic hybridization and fluorescence in situ hybridization (FISH) methods. [15][16][17][18] In an internal study, we assessed biopsy specimens showing high-grade dysplasia and cancer with FISH probes to 35 unique loci and identified 2 loci, the 3q26 region (comprising H-TERC gene) and the 8q24 region (comprising c-MYC gene), which showed highest frequency of copy number gains in high-grade dysplasia and cancer. Because these loci are frequently altered in cervical cancer tumorigenesis, 16,17,19,20 we hypothesized that they might be useful markers for the detection of cervical dysplasia and carcinoma.…”

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confidence: 99%

Chromosomal Biomarkers for Detection of Human Papillomavirus Associated Genomic Instability in Epithelial Cells of Cervical Cytology Specimens

Соколова

Algeciras‐Schimnich

Song

et al. 2007

The Journal of Molecular Diagnostics

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The goal of this study was to compare how accumulation of chromosomal aberrations in human papillomavirus (HPV)-infected cells correlates with the severity of cervical dysplastic lesions. We assessed the frequency of genomic alterations for 35 different loci in a pilot biopsy study and selected two loci (3q26 and 8q24) with the highest frequency of copy number gains found in high-grade dysplasia and cancer. These probes were labeled with gold and red fluorophores and combined with HPV biotin-labeled probes for subsequent detection using a tyramide signal amplification system with a green fluorophore. Cells that were both HPV positive and chromosomally abnormal were designated as "double-positive cells." Cervical cytology specimens from 235 patients were used for this blinded study. In the last decade, the etiological role of human papillomavirus (HPV) infection in the development of cervical dysplasia and cancer has been well established.1-4 The frequency of HPV infection in women with a diagnosis of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL) is approximately 50, 80, and 95%, respectively. 5-7Still, only a fraction of HPV-infected women will develop high-grade lesions and cervical cancer. 8HPV infections compromise normal cellular proliferation through degradation of the tumor suppressor proteins p53 and pRB by viral proteins E6 and E7, respectively. In addition, HPV infection has been shown to induce abnormal centrosome duplication early in the infection process.9 -12 HPV infection of replicating immature cells prevents epithelial maturation and differentiation, leading to continued replication and accumulation of genetic abnormalities. 2,13,14 Chromosomal instability at a numerical or structural level is a hallmark of malignant tumors.9 Deletion, duplication, and amplification of various genomic regions have been demonstrated in cervical cancer by comparative genomic hybridization and fluorescence in situ hybridization (FISH) methods. [15][16][17][18] In an internal study, we assessed biopsy specimens showing high-grade dysplasia and cancer with FISH probes to 35 unique loci and identified 2 loci, the 3q26 region (comprising H-TERC gene) and the 8q24 region (comprising c-MYC gene), which showed highest frequency of copy number gains in high-grade dysplasia and cancer. Because these loci are frequently altered in cervical cancer tumorigenesis, 16,17,19,20 we hypothesized that they might be useful markers for the detection of cervical dysplasia and carcinoma.To explore this further, we created a fluorescence in situ hybridization assay that allows for the simultaneous Supported by a grant from Abbott Molecular (to K.C.H.).

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“…approach has been applied to many different tumor types, including cervical cancer, mainly using repetitive probe sequences that detect the centromeres of human chromosomes. [21][22][23][24] We have now devised a multicolor fluorescence in situ hybridization (FISH) assay using three specific DNA probes. The design of the probe panel was solely based on the pattern of genomic imbalances in cervical cancers as detected by comparative genomic hybridization (CGH).…”

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Detection of Genomic Amplification of the Human Telomerase Gene (TERC) in Cytologic Specimens as a Genetic Test for the Diagnosis of Cervical Dysplasia

Heselmeyer‐Haddad

Janz

Castle

et al. 2003

The American Journal of Pathology

110

119

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Invasive cervical carcinomas frequently reveal additional copies of the long arm of chromosome 3. The detection of this genetic aberration in diagnostic samples could therefore complement the morphological interpretation. We have developed a triple-color DNA probe set for the visualization of chromosomal copy number changes directly in thin-layer cervical cytology slides by fluorescence in situ hybridization. The probe set consists of a BAC contig that contains sequences for the RNA component of the human telomerase gene (TERC) on chromosome band 3q26, and repeat sequences specific for the centromeres of chromosomes 3 and 7 as controls. In a blinded study, we analyzed 57 thin-layer slides that had been rigorously screened and classified as normal (n ‫؍‬ 13), atypical squamous cells (ASC, n ‫؍‬ 5), low-grade squamous intraepithelial lesions (LSIL, n ‫؍‬ 14), and highgrade squamous intraepithelial lesions ( Cytologic screening 1 has greatly reduced incidence and mortality of cervical cancer in industrialized nations.2 In developing countries, however, cervical cancer remains a health problem of tremendous proportions. If detected in a timely manner, cervical cancer precursors, especially high-grade squamous intraepithelial lesions (HSILs) can be effectively treated, sparing patients the morbidity and mortality resulting from invasive cancer. Despite its success as a public health measure, a single cytologic examination is relatively insensitive, poorly reproducible and frequently yields equivocal results. Inadequate sampling, the scarcity of aberrant cells in some samples and the subjectivity of morphological interpretation are recognized limitations of cytology. 2,3 In addition, equivocal and mild cytologic abnormalities are extremely common in young women, but most of these lesions regress spontaneously, even when caused by oncogenic types of human papillomaviruses, 4,5 which play a crucial role in the pathogenesis of cervical cancer. 6,7 This has prompted efforts to discover other biomarkers and other screening techniques with the potential to supplement cytologic screening. 8 -13

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Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia

Cited by 25 publications

References 11 publications

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

Chromosomal Biomarkers for Detection of Human Papillomavirus Associated Genomic Instability in Epithelial Cells of Cervical Cytology Specimens

Detection of Genomic Amplification of the Human Telomerase Gene (TERC) in Cytologic Specimens as a Genetic Test for the Diagnosis of Cervical Dysplasia

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