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液基薄层宫颈样本中伴有鳞状上皮内病变的P53、PTEN、FAS(CD95)、P16INK4A及HPV L1主要衣壳蛋白的免疫细胞化学表达

"Immunocytochemical expression of P53, PTEN, FAS (CD95), P16INK4A and HPV L1 major capsid proteins in ThinPrep cervical samples with squamous intraepithelial lesions".

作者信息

Grapsa D, Frangou-Plemenou M, Kondi-Pafiti A, Stergiou E, Nicolopoulou-Stamati P, Patsouris E, Chelidonis G, Athanassiadou P

机构信息

Cytopathology Department, LAIKO Athens General Hospital, Athens, Greece.

出版信息

Diagn Cytopathol. 2014 Jun;42(6):465-75. doi: 10.1002/dc.23003. Epub 2013 Jun 1.

Abstract

The aim of this study was to further investigate the immunocytochemical expression of p53, PTEN, Fas, p16, and HPV L1 capsid proteins in cervical smears with low and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively). A total of 92 ThinPrep cervical samples, comprising 11 cases of HSIL, 61 cases of LSIL, and 20 negative cases were studied by immunocytochemical methods. The results obtained in LSIL cases were correlated with the available follow up data. Abnormal p53, PTEN, or Fas expression was found in a subset of HSIL cases, while positive expression for p16 was significantly associated with the diagnosis of HSIL (P < 0.0001, P = 0.001, P < 0.0001, and P < 0.0001, respectively). Among cases positive for p16 expression, the staining pattern was weak in 88.9% of LSIL cases and strong in 80% of HSIL cases (P < 0.0001). The p16 negative/L1 positive and p16 positive/L1 negative staining patterns were significantly associated with the presence of LSIL and HSIL, respectively (P < 0.0001). None of these markers had a significant prognostic value in LSIL cases (P > 0.05). Our results suggest that loss of PTEN or Fas expression and p53 overexpression may be involved in the process of neoplastic transformation of the cervical epithelium. Furthermore, negative or weak immunocytochemical staining for p16 in a Pap smear may strongly argue against the presence of a high grade lesion, while the combined p16/L1 staining pattern may be useful as a diagnostic adjunct for differentiating between LSIL and HSIL.

摘要

本研究的目的是进一步调查p53、PTEN、Fas、p16和人乳头瘤病毒1型(HPV L1)衣壳蛋白在分别患有低级别和高级别鳞状上皮内病变(分别为LSIL和HSIL)的宫颈涂片中的免疫细胞化学表达情况。采用免疫细胞化学方法对总共92例ThinPrep宫颈样本进行了研究,其中包括11例HSIL、61例LSIL和20例阴性病例。将LSIL病例获得的结果与现有的随访数据进行了关联分析。在一部分HSIL病例中发现了p53、PTEN或Fas的异常表达,而p16的阳性表达与HSIL的诊断显著相关(P分别<0.0001、P = 0.001、P < 0.0001和P < 0.0001)。在p16表达阳性的病例中,88.9%的LSIL病例染色模式较弱,80%的HSIL病例染色模式较强(P < 0.0001)。p16阴性/L1阳性和p16阳性/L1阴性染色模式分别与LSIL和HSIL的存在显著相关(P < 0.0001)。这些标志物在LSIL病例中均无显著的预后价值(P > 0.05)。我们的结果表明,PTEN或Fas表达缺失以及p53过表达可能参与了宫颈上皮的肿瘤转化过程。此外,巴氏涂片中p16免疫细胞化学染色阴性或弱阳性可能强烈提示不存在高级别病变,而联合的p16/L1染色模式可能作为区分LSIL和HSIL的诊断辅助手段。

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