p16(INK4a) overexpression is not linked to oncogenic human papillomaviruses in patients with high-grade urothelial cancer cells
| Autor: | Eric, Piaton, Jean-Sébastien, Casalegno, Anne-Sophie, Advenier, Myriam, Decaussin-Petrucci, Florence, Mege-Lechevallier, Alain, Ruffion, Yahia, Mekki |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Aged 80 and over Carcinoma Transitional Cell Genotype Papillomavirus Infections Cystoscopy Middle Aged Cystectomy Sensitivity and Specificity Cohort Studies Gene Expression Regulation Neoplastic Urinary Bladder Neoplasms DNA Viral Tumor Cells Cultured Humans Female Neoplasm Invasiveness Papillomaviridae Cyclin-Dependent Kinase Inhibitor p16 In Situ Hybridization Aged Neoplasm Staging |
| Zdroj: | Cancer cytopathology. 122(10) |
| ISSN: | 1934-6638 |
| Popis: | p16(INK4a) Is overexpressed in almost all precancerous and carcinomatous lesions of the uterine cervix, secondary to interference between high-risk human papillomaviruses (hr-HPVs) and the retinoblastoma gene product. Overexpression of p16(INK4a) has also been identified in patients with high-grade urothelial lesions, both cytologically and histologically. However, the etiological role of HPV has not been documented except in inverted papillomas, low-grade bladder tumors, and younger patients. We therefore attempted to verify if HPV DNA was detectable in p16(INK4a) -positive urothelial tumors.A total of 90 urinary cytology samples (33 negative/low-grade cases and 57 high-grade proliferations) were analyzed for p16(INK4a) and HPV DNA. HPV genotyping was performed by polymerase chain reaction using a low-density DNA microarray enabling the detection of 35 HPVs. A reasoned approach combining tissue genotyping and in situ hybridization (ISH) for hr-HPVs was used in patients with urinary HPV.Low-risk HPV (HPV-84) and hr-HPVs (HPV-16, -31, and -70) were detected. The prevalence of hr-HPVs in the urine was low: 5 of 82 patients (6.1%) and only 4 of 50 patients (8.0%) with high-grade urothelial malignancy. p16(INK4a) overexpression was noted in 49 high-grade samples (85.9%). In patients with p16(INK4a) -positive tumor cells and hr-HPV in the urine, HPV genotyping and ISH for hr-HPVs were negative in matched tissue sections.Our study shows a low prevalence of hr-HPVs in the urine of patients with high-grade urothelial malignancy. In those, p16(INK4a) overexpression occurs in the absence of demonstrable HPV DNA in the tissue sections, contrary to what is noted in gynecopathology. |
| Databáze: | OpenAIRE |
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