Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida dos Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
Pathol Oncol Res. 2012 Oct;18(4):929-37. doi: 10.1007/s12253-012-9523-y. Epub 2012 Mar 28.
Cervical cancer remains persistently the second most common malignancies among women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the estimate is for 18,430 new cases in 2011. Several types of molecular markers have been studied in carcinogenesis including proteins associated with apoptosis such as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and invasive squamous cell carcinomas (SCCs) of the uterine cervix and to verify a possible association with HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG-1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1 expression levels were significantly different between LSILs and HSILs (p = 0,014) and between LSILs and SCCs (p = 0,014). In regards to PARP-1 expression, we found significant differences between the expression levels in HSILs and SCCs (p = 0,022). No association was found between BAG-1 expression and the presence of HPV. However, a significant association was found between PARP-1 expression and HPV positivity in the HSILs group (p = 0,021). In conclusion our research suggests that BAG-1 expression could contribute to the differentiation between LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between HSIL HPV-related and SCC. Further studies are needed to clarify the molecular aspects of the relationship between PARP-1 expression and HPV infection, with potential applications for cervical cancer prediction.
宫颈癌仍然是全球女性中第二常见的恶性肿瘤,每年导致 50 万新发病例。仅在巴西,2011 年估计就有 18430 例新发病例。在癌变过程中,已经研究了几种类型的分子标志物,包括与细胞凋亡相关的蛋白,如 BAG-1 和 PARP-1。本研究旨在证明 BAG-1 和 PARP-1 在低级别鳞状上皮内病变(LSIL)、高级别鳞状上皮内病变(HSIL)和宫颈浸润性鳞状细胞癌(SCC)患者中的表达,并验证与 HPV 感染的可能相关性。通过免疫组织化学法分析了 50 例 LSIL、50 例 HSIL 和 50 例宫颈浸润性 SCC 组织中 BAG-1 和 PARP-1 的表达情况。采用 PCR 检测和分型 HPV DNA。LSIL 与 HSIL 之间(p=0.014)和 LSIL 与 SCC 之间(p=0.014)BAG-1 表达水平存在显著差异。关于 PARP-1 的表达,我们发现 HSIL 和 SCC 之间的表达水平存在显著差异(p=0.022)。BAG-1 表达与 HPV 存在之间未发现相关性。然而,在 HSIL 组中,PARP-1 表达与 HPV 阳性之间存在显著相关性(p=0.021)。总之,我们的研究表明 BAG-1 表达可能有助于 LSIL 与 HSIL/SCC 的区分,而 PARP-1 可能有助于区分与 HPV 相关的 HSIL 和 SCC。需要进一步研究以阐明 PARP-1 表达与 HPV 感染之间的分子关系,为宫颈癌预测提供潜在应用。