Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results

Abstract

Objective Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. Methods Chromosomal copy numbers at 3q26 (3q), 5p15 (5p), 20q13 (20q) and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥3 or ≥4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2+ and/or HSIL. Results The median number of cells with ≥3 signals increased with the severity of cervical lesion for each genomic locus (p-trend<0.02 for each locus). ROC analysis for the number of cells with ≥3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q, 5p, 20q and cen7, respectively, for the detection of CIN2+ and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. Conclusions Chromosomal gains at 3q, 5p, 20q and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

Triage of HPV positive women in cervical cancer screening

“…Several other markers have been proposed for specific detection of cervical precancers, including assays that detect chromosomal abnormalities, 63 HPV oncogene mRNA, 64, 65 or other cellular proliferation-associated proteins. 66 However, clinical data are very limited for these assays and they have not been formally evaluated in a HPV triage setting so far.…”

Amplification of 3q26 and 5p15 regions in cervical intraepithelial neoplasia

“…Searching through the PubMed it is possible to find approximately 40 studies evaluating the TERC gene in cervical carcinogenesis. There are only two studies evaluating the FISH analysis of telomerase genes as a complex. Except for the study by Takac et al., all others proved the importance of TERC gene testing.…”

Amplification of specific chromosomal regions assessed by fluorescent in situ hybridization on Pap smears to be added as screening tool for identifying women at risk of progressing to cervical cancer

“…All 200 cases were also subjected to FISH on the smear collected to assess clonal gain of four chromosomal loci commonly detected in HPV-associated cancers. 9 For each locus, nuclei with more than two signals were considered positive for gain. Although there were nuclei showing more than three signals for 3q26, they were all classified as >3 signals indicating the copy number variability.…”

“…8 Chromosomal abnormalities such as amplifications, deletions, and rearrangements of whole or parts of chromosomes are a hallmark of cancer and have been described in many tumor types. [9][10][11] The common chromosomal abnormalities identified in cervical cancer are gain of chromosomal regions 3q26 followed by 5p15, 20q13, and cen 7. 12,13 A new fluorescent in situ hybridization (FISH)-based test to identify these specific alterations has been developed.…”