Cavatorta Ana Laura, Di Gregorio Alejandra, Bugnon Valdano Marina, Marziali Federico, Cabral Mariela, Bottai Hebe, Cittadini Jorge, Nocito Ana Lia, Gardiol Daniela
Instituto de Biología Molecular y Celular de Rosario-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina.
Servicio de Ginecología, Hospital Provincial del Centenario, Rosario, Argentina.
Exp Mol Pathol. 2017 Feb;102(1):65-69. doi: 10.1016/j.yexmp.2016.12.008. Epub 2016 Dec 29.
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.
人类盘状大肿瘤抑制因子(DLG1)参与调节细胞极性和增殖,这表明上皮组织与细胞生长控制之间存在重要联系。然而,已证明DLG1在某些特定情况下可获得致癌特性。在这项研究中,我们评估了DLG1的表达及其对宫颈病变进展的影响,以探究这种极性蛋白在人类致癌过程中的潜在作用。我们通过免疫组织化学分析了30例诊断为低度鳞状上皮内病变(LSIL)的女性的宫颈活检组织中DLG1的表达情况。这些结果与患者在24个月随访期内的临床监测情况相关。我们的数据表明,所有DLG1染色模式与正常组织相似的LSIL患者显著更有可能病情消退(n = 23,模式I),而所有显示弥漫性且强烈DLG1染色的LSIL活检标本可能进展为高级别病变(n = 4,模式II)。最后,所有分析的持续性LSIL均显示DLG1染色不确定,呈弥漫性分布且强度不强(n = 3,模式III)。我们发现DLG1的表达模式与病变进展之间存在显著关联(p < 0.00001)。这项研究有助于了解DLG1的生物学功能,表明其表达可能在早期发育异常宫颈病变的进展中起重要作用,并提供预后信息。