Prediction of outcome in patients with low‐grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, <i>TERC</i>, and <i>MYC</i>

Obermann, Ellen C.; Prince, Spasenija Savic; Barascud, Audrey; Grilli, Bruno; Herzog, Michelle; Kaup, Daniela; Cathomas, Gieri; Tirri, Brigitte Frey; Zlobec, Inti; Wight, Edward; Bubendorf, Lukas

doi:10.1002/cncy.21280

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…In contrast to recent reports we were unable to identify TERC as a prognostic factor [15, 34–36]. Such discrepancy may be due to the use of different material since prior studies were entirely based on cytological specimens.…”

Section: Discussioncontrasting

confidence: 99%

“…Such discrepancy may be due to the use of different material since prior studies were entirely based on cytological specimens. Additionally, in contrast to our cohort, three studies [34–36] were based on the analysis of low-grade dysplasia solely and only one study [15] used CIN I and II lesions. Also, all authors used cut-off criteria different from our values.…”

Section: Discussionmentioning

confidence: 99%

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c-myccopy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

et al. 2014

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Cervical carcinoma develops from preneoplasia by a multistep process. Although most low-grade dysplastic lesions will regress without intervention and even high-grade changes exhibit a substantial rate of regression, a small percentage of dysplasia will progress over time. Thus, indicators are needed to estimate the biological risk and to help avoid overtreatment in women who desire to preserve fertility. In addition to the classical biomarkers, PCR-ELISA-determined HPV genotype and immunohistochemically assessed p16INK4a and Ki-67 expression, cells with integrated HPV and copy number gain of TERC and c-myc were quantified in a panel of 104 benign, intraepithelial neoplastic (CIN I, II, III) and cancerous lesions using fluorescence in situ hybridization. Optimal cut-off values were calculated; Kaplan-Meier curves and a Cox proportional hazard regression model were used to evaluate prognostic signatures. The assay reliably identified HPV integration, TERC and c-myc copy number gain as determined by comparisons with established biomarkers. All biomarker levels increased with the progression of the disease. However, only c-myc copy number gain independently prognosticated a low probability of dysplastic regression. Our results suggest that c-myc plays a key role in the process of dysplastic transformation and might thus be exploited for treatment and follow-up decision-making of cervical dysplasia.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

c-myccopy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

et al. 2014

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“…To avoid counting split signals as 2 signals, the distance between any 2 signals had to be at least the diameter of 1 signal, in order for them to be counted as individual signals. A case was considered positive for 3q26 amplification by having ≥5 locus-specific signals in at least 10% of the abnormal cells according to the criteria of Obermann et al [15]. Image acquisition and analysis were performed using Ikoniscope digital microscopy system automation (Konisys Inc., New Haven, Conn., USA) equipped with optical filters.…”

Section: Methodsmentioning

confidence: 99%

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Zappacosta

Ianieri²,

Buca³

et al. 2015

Acta Cytologica

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Objective: This study was designed to evaluate whether the adjunct of human telomerase RNA component (hTERC) fluorescence in situ hybridization (FISH) analysis to cytological diagnosis and human papillomavirus (HPV)-DNA testing may serve as a predictive marker for distinguishing cervical lesions destined to regress from those at high risk of progression towards invasive cancer. Study Design: hTERC FISH analysis was performed on 54 residual liquid-based cytology specimens obtained from women referred to colposcopy for the detection of atypical squamous cells of undetermined significance or worse (ASCUS+) lesions. Histological diagnosis was considered the gold standard and cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as the worst outcome. Results: Oncogenic HPV-DNA was found in 96.3% of the specimens. Among these, 38.5% revealed a CIN2+ diagnosis. hTERC gene amplification was detected in 37% of the cases; among these, 70% showed up as CIN2+. hTERC FISH analysis significantly improves the specificity and positive predictive value of HPV-DNA testing, thus differentiating patients with a CIN2+ diagnosis from those with a CIN2- diagnosis. Conclusions: Despite the limitation of a small study sample, our findings provide promising data, indicating the possible role of hTERC analysis in the assessment of the risk of developing cervical cancer. This approach would implement the specificity of DNA testing, avoiding overtreatment at the same time. Prospective follow-up studies are needed with the aim of introducing hTERC FISH into decision-making algorithms.

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“…No se encontraron diferencias estadísticas entre la frecuencia de integración de VPH16 o VPH18 y el diagnóstico histológico, lo que confirma la disrupción temprana en E2 de ambos genotipos de VPH-AR. Otro estudio, realizado en Suiza, encontró resultados similares 40 . En las lesiones pre-neoplásicas, encontramos una frecuencia de integración del VPH de 55,6 y de 65% en LIEBG y LIEAG, respectivamente.…”

Section: Infecciones De Transmisión Sexualunclassified

Detección e integración del virus del papiloma humano de alto riesgo en lesiones pre-neoplásicas en mujeres del sur de Chile: un estudio transversal

Ili,

López,

Reyes

et al. 2024

Rev. chil. infectol.

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Introducción: El virus del papiloma humano de alto riesgo (VPH-AR) es responsable del cáncer de cuello uterino y sus lesiones preneoplásicas. Los genotipos VPH16 y VPH18 son los más frecuentes en este cáncer. La integración del VPH-AR en el genoma de la célula hospedera es crucial en la carcinogénesis cervical, pero la etapa en que ocurre en la población chilena es incierta. Objetivo: Evaluar la integración de VPH16 y VPH18 en lesiones pre-neoplásicas de cuello uterino. Métodos: Se analizaron 108 muestras de raspados cervicales. El VPH se genotipificó mediante reacción de polimerasa en cadena (RPC) e hibridación no radiactiva. La integración de VPH16 y VPH18 se determinó por presencia del gen E2 mediante RPC. Resultados: VPH16 y VPH18 se detectaron en 36,1% y 12,0% de las muestras, respectivamente. El VPH16 se integró en 23,1% de los casos de VPH16, mientras que VPH18 se integró en 100% de las muestras positivas para este genotipo. Conclusiones: La integración VPH-AR es un evento temprano en la carcinogénesis cervical que ocurre en casi la mitad de las lesiones pre-neoplásicas y es más frecuente en VPH18 que en VPH16. La evaluación de la integración VPH-AR puede ser una herramienta útil para detectar el virus en la población chilena.Palabras clave: virus papiloma humano; lesiones cervicales; integración VPH.

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Prediction of outcome in patients with low‐grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

Cited by 6 publications

References 38 publications

c-myccopy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

c-myccopy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Detección e integración del virus del papiloma humano de alto riesgo en lesiones pre-neoplásicas en mujeres del sur de Chile: un estudio transversal

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