BACKGROUND: Genomic amplification of the human telomerase RNA gene (hTERC), located in the chromosome 3q26 region, has been documented in tumorigenesis. The present study was designed to detect hTERC amplification in cervical lesions and evaluate whether this might serve as a supportive biomarker to cytopathology or histopathology in the diagnosis of cervical lesions. METHODS: Liquid-based thin-layer cytopathologic examination and detection of amplification by fluorescence in situ hybridization (FISH) was conducted in 130 women, along with assessment of human papillomavirus DNA, colposcopy with biopsy, and histopathologic examination. RESULTS: In cytopathologic examinations, hTERC amplification rates for negative for intraepithelial lesion or malignancy (NILM),atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) cases were 0% (0/10), 4% (1/25), 20% (6/30), 77% (27/35), and 100% (10/10), respectively. The difference among abnormal cellular change groups was statistically significant (P< 0.05). In histopathologic examinations, hTERC amplification rates in normal squamous cell with or without inflammatory, cervical intraepithelial neoplasia 1 (CIN 1), CIN 2, CIN 3 and SCC cases were 3.8% (2/52), 18.2% (6/33), 66.7% (6/9), 84.6% (22/26), 100% (10/10), respectively. There were significant differences among CIN1, CIN2, CIN3 and SCC cases (P< 0.05). The hTERC amplification was more specific than HPV positivity in differentiating lowgrade from high-grade cervical disorders (specificity: 88.5% vs. 70.8%, P< 0.05). CONCLUSIONS: FISH detection of hTERC amplification could be an effective adjunct to cytopathologic or histopathologic examination for differential diagnosis of low- and high-grade cervical squamous cell disorders.
BACKGROUND: Genomic amplification of the human telomerase RNA gene (hTERC), located in the chromosome 3q26 region, has been documented in tumorigenesis. The present study was designed to detect hTERC amplification in cervical lesions and evaluate whether this might serve as a supportive biomarker to cytopathology or histopathology in the diagnosis of cervical lesions. METHODS: Liquid-based thin-layer cytopathologic examination and detection of amplification by fluorescence in situ hybridization (FISH) was conducted in 130 women, along with assessment of human papillomavirus DNA, colposcopy with biopsy, and histopathologic examination. RESULTS: In cytopathologic examinations, hTERC amplification rates for negative for intraepithelial lesion or malignancy (NILM),atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) cases were 0% (0/10), 4% (1/25), 20% (6/30), 77% (27/35), and 100% (10/10), respectively. The difference among abnormal cellular change groups was statistically significant (P< 0.05). In histopathologic examinations, hTERC amplification rates in normal squamous cell with or without inflammatory, cervical intraepithelial neoplasia 1 (CIN 1), CIN 2, CIN 3 and SCC cases were 3.8% (2/52), 18.2% (6/33), 66.7% (6/9), 84.6% (22/26), 100% (10/10), respectively. There were significant differences among CIN1, CIN2, CIN3 and SCC cases (P< 0.05). The hTERC amplification was more specific than HPV positivity in differentiating lowgrade from high-grade cervical disorders (specificity: 88.5% vs. 70.8%, P< 0.05). CONCLUSIONS: FISH detection of hTERC amplification could be an effective adjunct to cytopathologic or histopathologic examination for differential diagnosis of low- and high-grade cervical squamous cell disorders.
Authors: Patricia Luhn; Jane Houldsworth; Lynnette Cahill; Mark Schiffman; Philip E Castle; Rosemary E Zuna; S Terence Dunn; Michael A Gold; Joan Walker; Nicolas Wentzensen Journal: Gynecol Oncol Date: 2013-06-13 Impact factor: 5.482