Wright Thomas C, Compagno John, Romano Patricia, Grazioli Vittorio, Verma Yogita, Kershnar Eric, Tafas Triantafyllos, Kilpatrick Michael W
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, and Research Pathology Associates, Irvington, NY.
West Coast Pathology Laboratories, Hercules, CA.
Am J Obstet Gynecol. 2015 Jul;213(1):51.e1-51.e8. doi: 10.1016/j.ajog.2015.02.001. Epub 2015 Feb 4.
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.
在宫颈上皮内瘤变2级和3级（CIN 2,3）以及宫颈鳞状细胞癌中一直观察到3号染色体长臂（3q）增益。在液基细胞学标本中检测3q增益有许多潜在的临床用途，包括识别意义不明确的非典型鳞状细胞或低级别鳞状上皮内病变细胞学的女性亚组，这些女性患CIN 2,3的风险最高，因此最能从即时阴道镜检查中获益。本研究的目的是确定3q增益在鉴别CIN 2,3和正常情况时的敏感性和特异性。
收集了199名女性的剩余细胞学标本。采用液基细胞学（LBC）进行受试者选择，患有高级别鳞状上皮内病变或高级别鳞状上皮内病变且接受阴道镜检查并经活检确诊为CIN 2,3的女性组成疾病阳性组（n = 28），细胞学和高危人乳头瘤病毒（hrHPV）检测均为双阴性的女性组成疾病阴性组（n = 171）。从每个剩余的LBC标本制备一张玻片，使用针对3q26区域的特异性探针和7号染色体着丝粒的对照探针，通过荧光原位杂交分析3q增益。比较了两种确定3q增益的方法。第一种方法基于分析整个宫颈细胞学玻片，以确定是否存在3q基因座拷贝数高（>4个拷贝）的罕见细胞。第二种方法基于分析400个细胞，以确定3q基因座有3个或更多拷贝的细胞百分比。
采用基于检测3q基因座拷贝数高（>4个拷贝）的罕见细胞的方法，CIN 2,3女性的26个标本3q增益呈阳性，而171例hrHPV和细胞学均为阴性的女性标本无一例3q增益呈阳性。这意味着在鉴别CIN 2,3和正常情况时，敏感性为92.9%（95%置信区间[CI]，76.5 - 98.9%），特异性为100%（95% CI，97.8 - 100%），阳性预测值为100%（95% CI，86.7 - 100%），阴性预测值为98.8%（95% CI，95.9 - 99.8）。
这些数据支持3q增益在多种临床情况下对女性进行评估的潜在临床应用，包括意义不明确的非典型鳞状细胞、低级别鳞状上皮内病变以及hrHPV阳性的女性。
