Objective
Chromosome 3q gain has been consistently observed in cervical intraepithelial neoplasia
grades 2 and 3 (CIN 2,3) and squamous cell carcinomas of the cervix. There are a number
of potential clinical uses of testing for 3q gain in liquid cytology specimens, including
the identification of subsets of women with atypical squamous cells of undetermined
significance or low-grade squamous intraepithelial lesion cytology who are at greatest
risk of having CIN 2,3 and would thus benefit most from immediate colposcopy. The
objective of this study was to establish the sensitivity and specificity of 3q gain
for discriminating between CIN 2,3 and normal.
Study Design
Residual cytology specimens were collected from 199 women. Liquid-based cytology (LBC)
was used for the selection of subjects, with women with high-grade squamous intraepithelial
lesion or high-grade squamous intraepithelial lesion who had colposcopy and adjudicated
biopsy-confirmed CIN 2,3 forming the disease-positive group (n = 28) and women doubly
negative for both cytology and high-risk human papillomavirus (hrHPV) testing forming
the disease-negative group (n = 171). A single slide was prepared from each residual
LBC specimen and analyzed for 3q gain by fluorescent in situ hybridization, using
a probe specific for the 3q26 region and a control probe for the chromosome 7 centromere.
Two approaches were compared for the determination of 3q gain. The first was based
on the analysis of an entire cervical cytology slide for the presence of rare cells
with a high copy number (>4 copies) for the 3q locus. The second approach was based
on the analysis of 400 cells to determine the percentage with 3 or more copies of
the 3q locus.
Results
Using the approach based on the detection of rare cells with a high copy number (>4
copies) for the 3q locus, 26 of the specimens from women with CIN 2,3 and none of
the 171 specimens from women who were both hrHPV and cytology negative was positive
for 3q gain. This translates to a sensitivity of 92.9% (95% confidence interval [CI],
76.5–98.9%), a specificity of 100% (95% CI, 97.8–100%), a positive predictive value
of 100% (95% CI, 86.7–100%), and a negative predictive value of 98.8% (95% CI, 95.9–99.8),
for distinguishing CIN 2,3 from normal.
Conclusion
These data support the potential clinical use of 3q gain for the evaluation of women
in a number of clinical situations, including women with atypical squamous cells of
undetermined significance, low-grade squamous intraepithelial lesion, and those who
are hrHPV positive.
Key words
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References
- Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review.Ann Intern Med. 2000; 132: 810-819
- Human papillomavirus testing in the prevention of cervical cancer.J Natl Cancer Inst. 2011; 103: 368-383
- Regression of low-grade squamous intra-epithelial lesions in young women.Lancet. 2004; 364: 1678-1683
- The ALTS Group. Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial.J Natl Cancer Inst. 2000; 92: 397-402
- Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2.Obstet Gynecol. 2009; 113: 18-25
- Gain of the 3q26 region in cervicovaginal liquid-based pap preparations is associated with squamous intraepithelial lesions and squamous cell carcinoma.Gynecol Oncol. 2008; (ScienceDirect Online)
- Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q.Genes Chromosom Cancer. 1997; 19: 233-240
- Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer.J Pathol. 2006; 210: 412-419
- Chromosomal biomarkers for detection of human papillomavirus associated genomic instability in epithelial cells of cervical cytology specimens.J Mol Diag. 2007; 9: 604-611
- Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer.Am J Pathol. 2005; 166: 1229-1238
- Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears.Am J Pathol. 2009; 175: 1831-1847
- Gain of 3q26: a genetic marker in low-grade squamous intraepithelial lesions (LSIL) of the uterine cervix.Gynecol Oncol. 2009; 114: 80-83
- The use of polymerase chain reaction amplification for the detection of genital human papillomaviruses.in: Furth M. Greaves M. Molecular diagnostics of human cancer. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY1989: 209-214
- Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia.Am J Pathol. 2003; 163: 1405-1416
- Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.Gynecol Oncol. 2013; 130: 595-600
- Unpacking the 2×2 table.Heart Lung. 2013; 42: 221-226
- Automated detection of rara fetal cells in maternal blood: eliminating the false-positive XY signals in XX pregnancies.Am J Obstet Gynecol. 2004; 190: 1571-1581
- Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytologic finding.Am J Obstet Gynecol. 2010; 202: 581.e1-581.e5
- Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study.Lancet Oncol. 2011; 12: 880-890
- 3q26 amplification is an effective negative triage test for LSIL: a historical prospective study.PLoS One. 2012; 7: e39101
- Role of chromosome 3q26 in predicting progression of cervical dysplasia.Int J Gynecol Cancer. 2012; 22: 742-747
Article info
Publication history
Published online: February 04, 2015
Accepted:
February 2,
2015
Received in revised form:
January 2,
2015
Received:
June 27,
2014
Footnotes
Y.V., E.K., T.T., and M.W.K. are employed by Ikonisys Inc. The other authors report no conflict of interest.
Cite this article as: Wright TC, Compagno J, Romano P, et al. Amplification of the 3q chromosomal region as a specific marker in cervical cancer. Am J Obstet Gynecol 2015;213:51.e1-8.
Identification
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© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
