DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions |
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Authors: | Ana Laura Cavatorta Alejandra Di Gregorio Marina Bugnon Valdano Federico Marziali Mariela Cabral Hebe Bottai Jorge Cittadini Ana Lia Nocito Daniela Gardiol |
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Affiliation: | 1. Instituto de Biología Molecular y Celular de Rosario-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina;2. Servicio de Ginecología, Hospital Provincial del Centenario, Rosario, Argentina;3. Área Estadística y Procesamiento de Datos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina;4. Cátedra de Anatomía y Fisiología Patológicas, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina |
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Abstract: | Human Discs large tumour suppressor (DLG1) participates in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. However, it was demonstrated that DLG1 could acquire oncogenic attributes in some specific contexts. In this work, we evaluated the expression of DLG1 and its contribution to the progress of cervical lesions in order to investigate a potential role of this polarity protein in human oncogenic processes.We analyzed cervical biopsies from women with low-grade squamous intraepithelial lesion (LSIL) diagnosis (n = 30), for DLG1 expression by immunohistochemistry. These results were correlated with the clinical monitoring of the patients during a 24-month follow-up period. Our data indicate that while all LSIL patients with a DLG1 staining pattern similar to normal tissues are significantly more likely to regress (n = 23, Pattern I), all LSIL biopsy specimens showing a diffuse and intense DLG1 staining likely progress to high-grade lesions (n = 4, Pattern II). Finally, all persistent LSIL analyzed showed an undetermined DLG1 staining, with a diffuse distribution without a strong intensity (n = 3, Pattern III). We found a significant association between the expression pattern of DLG1 and the evolution of the lesion (p < 0.00001).This work contributes to the knowledge of DLG1 biological functions, suggesting that its expression may have an important role in the progression of early dysplastic cervical lesions, giving prognostic information. |
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Keywords: | DLG1 human Discs large HPV Human papillomavirus MAGUKs membrane-associated guanylate kinase homologues PDZ PSD-95/DLG/ZO-1 domains LSIL low-grade squamous intraepithelial lesions HSIL high-grade squamous intraepithelial lesions CIN cervical intraepithelial neoplasia IHC immunohistochemistry PAP Papanicolaou MAGI-2 WW and PDZ domain containing protein 2 DLG1 LSIL progression Cervical cancer Immunohistochemistry |
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