Mauro Laura V, Dalurzo Mercedes, Smith David, Lastiri Jose, Vasallo Bartolome, Joffei Elisa Bal de Kier, Pallotta Maria Guadalupe, Puricelli Lydia
Area Investigación, Instituto de Oncología Angel H. Roffo, Buenos Aires, Argentina.
Medicina (B Aires). 2008;68(3):205-12.
Although early-stage non-small-cell lung carcinoma (NSCLC) patients have a relative by favorable prognosis, the risk of a bad outcome remains substantial. Identification of reliable prognostic markers for disease recurrence and death has meaningful clinical application. Retinoids are involved in cell growth and differentiation and may antagonize cancer progression. Their effects are mediated through nuclear receptors called Retinoic Acid Receptor (RAR) and regulated by molecules such as Cellular Retinol-Binding Protein 1 (CRBP1) that function in retinol storage. The aim of this work was to analyze by immunohistochemistry the expression patterns of RARbeta and CRBP1, involved in retinoid-mediated signaling, in the tumoral tissue of a cohort of stage I/II NSCLC patients (n = 49) who underwent a successful surgical resection. Prognostic evaluation was performed with the multivariate Cox proportional hazard model: 44.9% of tumors were positive for RARbeta staining at cytoplasmic level, while 34.7% showed nuclear staining. CRBP1 staining was observed in 61.2% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T and N (stage), histopathology and p53 expression. Univariate analysis showed a significant association between positive cytoplasmatic expression of RARbeta with shorter overall survival (Log-rank test 4.17, p = 0.0412). Multivariate studies indicated that RARbeta expression was not influenced by other clinical pathological parameters. In conclusion, in this cohort of stage I and II NSCLC, only the expression of RARbeta at cytoplasmatic level is a significant independent unfavorable prognostic factor.
尽管早期非小细胞肺癌(NSCLC)患者的预后相对较好,但不良结局的风险仍然很大。识别疾病复发和死亡的可靠预后标志物具有重要的临床应用价值。维甲酸参与细胞生长和分化,可能拮抗癌症进展。它们的作用通过称为视黄酸受体(RAR)的核受体介导,并受视黄醇储存相关分子如细胞视黄醇结合蛋白1(CRBP1)的调节。本研究的目的是通过免疫组织化学分析参与维甲酸介导信号传导的RARβ和CRBP1在一组接受成功手术切除的I/II期NSCLC患者(n = 49)肿瘤组织中的表达模式。采用多变量Cox比例风险模型进行预后评估:44.9%的肿瘤在细胞质水平RARβ染色呈阳性,而34.7%呈核染色阳性。61.2%的肺肿瘤观察到CRBP1染色。在所研究分子表达细胞数量与包括性别、T和N(分期)、组织病理学和p53表达在内的临床病理特征之间未发现相关性。单变量分析显示RARβ阳性细胞质表达与较短的总生存期之间存在显著关联(对数秩检验4.17,p = 0.0412)。多变量研究表明RARβ表达不受其他临床病理参数影响。总之,在这组I期和II期NSCLC中,仅细胞质水平的RARβ表达是一个显著的独立不良预后因素。