High levels of p53 expression correlate with DNA aneuploidy in (pre)malignancies of the vulva
| Autor: | Leon F A G Massuger, Johan Bulten, Irene A.M. van der Avoort, Léon C van Kempen, Hedwig P. van de Nieuwenhof, Joanne A. de Hullu, Jeroen van der Laak, Piet J. Slootweg, Irene Otte-Höller, Ella Nirmala |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Vulvar Squamous Cell Carcinoma Aneuploidy Biology Lichen sclerosus Epithelium Vulvar Lichen Sclerosus Vulva Pathology and Forensic Medicine Translational research [ONCOL 3] Carcinoma medicine Humans DNA Image Cytometry Aged Cell Proliferation Aged 80 and over Vulvar Neoplasms integumentary system DNA DNA Neoplasm Middle Aged medicine.disease female genital diseases and pregnancy complications stomatognathic diseases medicine.anatomical_structure Carcinoma Squamous Cell Papilloma Female Tumor Suppressor Protein p53 Precancerous Conditions Cytometry Carcinoma in Situ |
| Zdroj: | Human Pathology, 41, 10, pp. 1475-85 Human Pathology, 41, 1475-85 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/j.humpath.2009.12.015 |
| Popis: | Contains fulltext : 88355.pdf (Publisher’s version ) (Open Access) The molecular pathogenesis of human papilloma virus-unrelated vulvar squamous cell carcinoma is not well known. Whether malignant progression of lichen sclerosus and differentiated vulvar intraepithelial neoplasia to vulvar squamous cell carcinoma could be accompanied by altered DNA content has not been studied extensively. DNA content in isolated nuclei of microdissected normal vulvar epithelium (n = 2), lichen sclerosus (n = 9), differentiated vulvar intraepithelial neoplasia (n = 13), and squamous cell carcinoma (n = 17) from 22 patients was measured via DNA image cytometry. For additional analysis, 6 differentiated vulvar intraepithelial neoplasia lesions were selected, bringing the number of patients to 28. p53 expression was determined by immunohistochemistry on consecutive tissue sections. Thirty-eight percent (5/13) of differentiated vulvar intraepithelial neoplasia lesions and 65% (11/17) of squamous cell carcinomas were DNA aneuploid or tetraploid. In lesions that contained differentiated vulvar intraepithelial neoplasia and adjacent squamous cell carcinoma, the ploidy status of differentiated vulvar intraepithelial neoplasia did not exceed that of squamous cell carcinoma. We observed a strong correlation between high p53 expression and DNA aneuploidy. This relation was also present at the level of a single nucleus, measured by sequential image cytometry of p53 immunohistochemistry followed by DNA image cytometry on formalin-fixed tissue sections. Similarly, we found p53-positive nonproliferating cells with increased DNA content in the superficial compartment of 6 additional solitary differentiated vulvar intraepithelial neoplasia lesions that were not associated with squamous cell carcinoma, indicating ascending aneuploid cells from the basal compartment. DNA ploidy measurements suggest that differentiated vulvar intraepithelial neoplasia has a higher malignant potential than lichen sclerosus and thus is a more likely precursor of squamous cell carcinoma. Furthermore, high p53 expression correlates with increased DNA content and aneuploidy; but it requires further research to unveil a possible causal relation. 01 oktober 2010 |
| Databáze: | OpenAIRE |
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