Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
Virchows Arch. 2013 Jul;463(1):31-9. doi: 10.1007/s00428-013-1438-9. Epub 2013 Jun 9.
PAR-4 is a tumor suppressor protein with a pro-apoptotic function and down-regulation of PAR-4 is seen in a variety of tumors. PHLDA1 gene overexpression has been shown to reduce cell proliferation and induce cell death in a variety of cell types. In this study, 229 cases of oral squamous cell carcinoma (OSCC), arranged in a tissue microarray, were analyzed by immunohistochemistry. PAR-4 expression was predominantly moderate to strong and expression of PHLDA1 was predominantly negative or weak. Cytoplasmic expression of PAR-4 was associated with advanced clinical stage. Expression of PHLDA1 was associated with advanced clinical stage of the tumour. Five-year overall and disease-free survival rates differed significantly between cases that did and cases that did not express PHLDA1, and by multivariate analysis, expression of PHLDA1 and PAR-4 were independent prognostic factors in OSCC patients. Expression of PAR-4 and PHLDA1 is altered in OSCC and might be a valuable prognostic indicator for this disease.
PAR-4 是一种具有促凋亡功能的肿瘤抑制蛋白,在多种肿瘤中观察到 PAR-4 的下调。PHLDA1 基因的过表达已被证明可减少多种细胞类型的细胞增殖并诱导细胞死亡。在这项研究中,通过免疫组织化学分析了 229 例口腔鳞状细胞癌 (OSCC) 组织微阵列。PAR-4 的表达主要为中等到强,而 PHLDA1 的表达主要为阴性或弱阳性。PAR-4 的细胞质表达与临床分期较晚有关。PHLDA1 的表达与肿瘤的临床分期较晚有关。在表达和不表达 PHLDA1 的病例之间,5 年总生存率和无病生存率有显著差异,多变量分析表明,在 OSCC 患者中,PHLDA1 和 PAR-4 的表达是独立的预后因素。PAR-4 和 PHLDA1 在 OSCC 中的表达发生改变,可能是该疾病有价值的预后指标。