Fluorescence in Situ Hybridization in Cervical Smears: Detection of Numerical Aberrations of Chromosomes 7, 3, and X and Relationship to HPV Infection

Mian, Christine; Bancher, Dagmar; Kohlberger, Petra; Kainz, Christian; Haitel, Andrea; Czerwenka, K.; Stani, Josefine; Breitenecker, G.; Wiener, H.

doi:10.1006/gyno.1999.5522

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…Likewise, a gain of the long arm of chromosome 3 (3q) is found in 85% of cervical cancers (52)(53)(54)(55). The percentage of cells with this cytogenetic alteration increases with the degree of cellular dysplasia (21) and occurs before transition to overt invasive disease (56,57).…”

Section: Discussionmentioning

confidence: 99%

E6 and E7 Oncoproteins Induce Distinct Patterns of Chromosomal Aneuploidy in Skin Tumors from Transgenic Mice

et al. 2004

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Inactivation of the tumor suppressor genes p53 and Rb are two of the most common genetic alterations in cancer cells. We use a mouse model to dissect the consequences of compromising the function of either of these genes on the maintenance of genomic stability. Thirteen cell lines established from skin tumors of mice expressing either the E6 or E7 oncoprotein of the human papillomavirus (HPV) type 16 under control of the keratin 14 promoter were analyzed by comparative genomic hybridization, spectral karyotyping and fluorescence in situ hybridization, reverse transcription-PCR, and mutation analysis. Deducing from the wealth of molecular cytogenetic data available from human cancers, we hypothesized that the more benign tumors in mice expressing E7 would be distinct from the more aggressive lesions in E6 transgenic mice. Tumorigenesis in E6-expressing mice required specifically the selection and maintenance of cells with extra copies of chromosome 6. Aneuploidy of chromosome 6 was independent of activating mutations in H-ras on chromosome 7. Expression of either E6 or E7 resulted in centrosome aberrations, indicating that each viral oncoprotein interferes independently with the centrosome cycle. Although centrosome aberrations are consistent with development of aneuploidy, no direct correlation was evident between the degree of aneuploidy and the percentage of cells with aberrant centrosomes. Our results show that although aneuploidy and centrosome aberrations are present in tumor cells from mice expressing either E6 or E7, tumorigenesis via E6 requires copy number increases of mouse chromosome 6, which is partially orthologous to human chromosome 3q, a region gained in HPVassociated carcinomas.

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Section: Discussionmentioning

confidence: 99%

E6 and E7 Oncoproteins Induce Distinct Patterns of Chromosomal Aneuploidy in Skin Tumors from Transgenic Mice

et al. 2004

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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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confidence: 99%

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

111

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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“…We and others used fluorescence in situ hybridisation (FISH) to sensitively detect tumour cells regularly characterised by numeric chromosomal aberrations (Fiegl et al, 2000(Fiegl et al, , 2004van Oostenbrugge et al, 2000). By identification of tumour-associated aneuploidy, FISH analysis has been successfully applied in tumour aspirates, urine, cerebrospinal fluid, cervical smears, sputum, and effusions (Cajulis et al, 1994;Chen et al, 1995;Ichikawa et al, 1996;Schenk et al, 1997;Mian et al, 1999;Fiegl et al, 2000Fiegl et al, , 2004van Oostenbrugge et al, 2000).…”

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Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH)

et al. 2004

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Diagnosis of malignant cells in effusions is important for staging procedures and resulting therapeutic decisions. Cytodiagnostics in effusions is sometimes difficult since reactive mesothelial cells can mimic malignant cells. We used fluorescence in situ hybridisation (FISH) in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations in effusion cells as markers of malignancy, to raise the diagnostic yield. Cytologic and FISH evaluations -by using probes representing several chromosomes always including chromosomes 11 and 17 -were performed in 358 effusion fluids. Cytology was positive for malignancy in 44.4% of all effusions, whereas FISH was positive in 53.9% (P ¼ 0.0001). The combination of cytology and FISH was diagnostic for malignancy in 60.9% of effusions. Diagnostic superiority of FISH was demonstrated in effusions from breast cancer, lung cancer, pancreatic cancer, and in effusions from the entire group of gynaecological and gastrointestinal carcinomas. In transudates (effusion protein o2.5 g dl À1 ), malignant cells were detectable by cytology, FISH, and combined use of both methods in 18.6, 30, and 37.1% of effusions, respectively, suggesting that cytologic and molecular analysis should be performed also with transudates. In conclusion, FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting malignant cells in effusions.

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Fluorescence in Situ Hybridization in Cervical Smears: Detection of Numerical Aberrations of Chromosomes 7, 3, and X and Relationship to HPV Infection

Cited by 23 publications

References 19 publications

E6 and E7 Oncoproteins Induce Distinct Patterns of Chromosomal Aneuploidy in Skin Tumors from Transgenic Mice

E6 and E7 Oncoproteins Induce Distinct Patterns of Chromosomal Aneuploidy in Skin Tumors from Transgenic Mice

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

Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH)

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