Amplification of the 3q chromosomal region as a specific marker in cervical cancer

• Published in: American journal of obstetrics and gynecology Vol. 213; no. 1; pp. 51.e1 - 51.e8
• Main Authors: Wright, Thomas C., Compagno, John, Romano, Patricia, Grazioli, Vittorio, Verma, Yogita, Kershnar, Eric, Tafas, Triantafyllos, Kilpatrick, Michael W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: 3q gain; Algorithms; Atypical Squamous Cells of the Cervix; atypical squamous cells of undetermined significance; Cervical Intraepithelial Neoplasia - genetics; cervical intraepithelial neoplasia grades 2 and 3; Chromosomes, Human, Pair 3 - genetics; DNA Probes; Female; Gene Dosage; high-grade squamous intraepithelial lesion; high-risk human papillomavirus; Humans; In Situ Hybridization, Fluorescence; low-grade squamous intraepithelial lesion; Obstetrics and Gynecology; Precancerous Conditions - genetics; Sensitivity and Specificity; squamous cell carcinomas; Squamous Intraepithelial Lesions of the Cervix - genetics; Uterine Cervical Neoplasms - genetics; cervical intraepithelial neoplasia grades 2 and 3; low-grade squamous intraepithelial lesion; high-risk human papillomavirus; 3q gain; atypical squamous cells of undetermined significance; squamous cell carcinomas; high-grade squamous intraepithelial lesion
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2015.02.001

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. 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. 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. 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.