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DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions
Authors:Ana Laura Cavatorta  Alejandra Di Gregorio  Marina Bugnon Valdano  Federico Marziali  Mariela Cabral  Hebe Bottai  Jorge Cittadini  Ana Lia Nocito  Daniela Gardiol
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
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.
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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