Gabriel Boris, zur Hausen Axel, Stickeler Elmar, Dietz Carola, Gitsch Gerald, Fischer Dagmar-C, Bouda Jiri, Tempfer Clemens, Hasenburg Annette
Departments of Obstetrics and Gynecology and Pathology, Freiburg University Medical Center, Freiburg, Germany.
Clin Cancer Res. 2006 Apr 15;12(8):2476-83. doi: 10.1158/1078-0432.CCR-05-1867.
The pp125 focal adhesion kinase (FAK) plays a pivotal role in tumor cell signaling. FAK expression has been linked to tumor cell invasion and metastasis, but data on cervical cancer are inconclusive. Our goal was to investigate FAK expression in cervical cancer and to assess whether its expression correlates with prognosis.
FAK expression was examined using immunohistochemistry with sections from 162 resected cervical cancer specimens. Kaplan-Meier survival curves were used to determine the significance of FAK expression in the prognosis of cervical cancer patients.
Specific FAK expression was found in the tumor cells, whereas normal cervical epithelium showed barely any FAK expression. Of 162 invasive cervical cancer specimens, 55 (34%) revealed weak expression of FAK, whereas moderate and strong expression was found in 63 (39%) and 44 (27%) tumors, respectively. Patients with tumors expressing weak amounts of FAK were characterized by a significantly poorer overall survival compared with those with moderate and high intratumoral FAK expression (P = 0.002). Weak expression of FAK correlated with pelvic lymph node metastasis (P = 0.026) and recurrent disease (P = 0.013). Multivariate Cox regression analysis revealed decreased FAK expression and pelvic lymph node metastasis to be significant independent factors predictive of poor disease outcome (hazard ratio, 0.36; P = 0.005; hazard ratio, 2.38; P = 0.018, respectively).
Weak expression of FAK in invasive cervical cancer is a strong independent predictor of poor patient outcome. Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool identifying patients at high risk even at an early clinical stage.
pp125粘着斑激酶（FAK）在肿瘤细胞信号传导中起关键作用。FAK表达与肿瘤细胞侵袭和转移有关，但关于宫颈癌的数据尚无定论。我们的目标是研究FAK在宫颈癌中的表达，并评估其表达是否与预后相关。
采用免疫组织化学方法检测162例切除的宫颈癌标本切片中的FAK表达。用Kaplan-Meier生存曲线确定FAK表达在宫颈癌患者预后中的意义。
在肿瘤细胞中发现了特异性的FAK表达，而正常宫颈上皮几乎没有FAK表达。在162例浸润性宫颈癌标本中，55例（34%）显示FAK弱表达，63例（39%）和44例（27%）肿瘤分别显示中度和强表达。与肿瘤内FAK表达中度和高度的患者相比，FAK表达量低的患者总生存率显著较差（P = 0.002）。FAK弱表达与盆腔淋巴结转移（P = 0.026）和疾病复发（P = 0.013）相关。多变量Cox回归分析显示，FAK表达降低和盆腔淋巴结转移是预测疾病预后不良的重要独立因素（风险比分别为0.36；P = 0.005；风险比为2.38；P = 0.018）。
浸润性宫颈癌中FAK弱表达是患者预后不良的有力独立预测指标。有必要进一步研究以阐明FAK表达分析是否是一种即使在临床早期也能识别高危患者的合适工具。
