关键词: focal adhesion kinase kidney tumor paxillin renal cell carcinoma src tyrosine kinase

来  源:   DOI:10.7759/cureus.62706   PDF(Pubmed)

Abstract:
OBJECTIVE: The complex focal adhesion kinase (FAK)/Src and paxillin seem to play a key role in the pathogenesis and progression of cancer. The aim of this study is to evaluate the expression of these proteins in renal cell carcinomas (RCCs), considering the immunoreactive score (IRS), the positivity and the intensity, and to find any association with patients\' clinical characteristics, histologic type and other pathological features that imply a possible pathophysiological or prognostic role of FAK/Src and paxillin in RCC.
METHODS: Patients with RCC who had undergone partial or radical nephrectomy from January 2009 to September 2010 were eligible for this retrospective cross-sectional study. The immunohistochemical expression of FAK, Src and paxillin proteins in formalin-fixed paraffin-embedded tumour tissue was analysed in association with various clinicopathological features.
RESULTS: Out of ninety patients, 58 had clear cell renal carcinoma, 15 had papillary, 11 had chromophobe and six had unclassified RCC. FAK, Src and paxillin were expressed in 55.6%, 32.2% and 18.9% of all cases, respectively. In univariate analysis, FAK positivity and IRS were more likely in patients with papillary and chromophobe histologic type versus clear cell RCC (p<0.005), Src positivity and IRS presented more frequently in stage T3 versus T1 (p<0.005) and paxillin positivity was more likely in patients with stage T3 versus T2 (p=0.021) and grades 3-4 versus grade 2 (p=0.013). Paxillin-IRS was not associated with any clinicopathological features. The same associations were also reproduced in the multifactorial analysis for the FAK and Src positivity and IRS, while it was found that paxillin positivity and IRS were associated with the female gender (p=0.052, p=0.024), and were higher in grades 3-4 versus grade 2 (p=0.022, p=0.020).
CONCLUSIONS: Our study suggests that RCC shows immunohistochemical expression of FAK, Src and paxillin proteins, and this expression varies in relation to the histologic type, the stage and the stage/grade/gender, respectively. These findings imply a possible involvement of the FAK/Src signalling pathway in the pathogenesis and progression of cancer in RCC, providing future perspectives for targeted therapies with inhibitors.
摘要:
目的:复合粘着斑激酶(FAK)/Src和桩蛋白似乎在癌症的发病和进展中起关键作用。这项研究的目的是评估这些蛋白质在肾细胞癌(RCC)中的表达,考虑到免疫反应性评分(IRS),积极性和强度,并发现与患者临床特征的任何关联,组织学类型和其他病理特征暗示FAK/Src和桩蛋白在RCC中可能具有病理生理或预后作用。
方法:2009年1月至2010年9月接受部分或根治性肾切除术的RCC患者符合这项回顾性横断面研究的条件。FAK的免疫组化表达,与各种临床病理特征相关,分析了福尔马林固定的石蜡包埋的肿瘤组织中的Src和paxillin蛋白。
结果:在90名患者中,58例肾透明细胞癌,15有乳头状,11例具有发色性细胞,6例具有未分类的RCC。FAK,Src和paxillin表达率为55.6%,所有病例的32.2%和18.9%,分别。在单变量分析中,与透明细胞RCC相比,乳头状和发色组织学类型的患者更可能出现FAK阳性和IRS(p<0.005),Src阳性和IRS在T3期与T1期(p<0.005)中更常见,而在T3期与T2期(p=0.021)和3-4级与2级(p=0.013)的患者中,桩蛋白阳性的可能性更高。Paxillin-IRS与任何临床病理特征无关。在FAK和Src阳性和IRS的多因素分析中也再现了相同的关联,虽然发现paxillin阳性和IRS与女性相关(p=0.052,p=0.024),3-4年级高于2年级(p=0.022,p=0.020)。
结论:我们的研究表明RCC显示FAK的免疫组织化学表达,Src和桩蛋白,这种表达与组织学类型有关,舞台和舞台/年级/性别,分别。这些发现暗示FAK/Src信号通路可能参与RCC中癌症的发病机制和进展。为抑制剂靶向治疗提供未来前景。
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