Department of Gynaecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hum Pathol. 2010 Dec;41(12):1735-41. doi: 10.1016/j.humpath.2010.04.017.
The objective of this study is to correlate the expression of epidermal growth factor receptor (EGFR) components with clinical behavior of early-stage cervical cancer. Tissue samples of 336 consecutive Federation of International Gynecologists and Obstetricians stage IB-IIA cervical cancer patients all treated primarily by radical surgery were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. As representatives for the EGFR pathway, expression of EGFR, pEGFR, PTEN, pAKT, and pERK was assessed by immunohistochemistry on tissue microarrays. Positive immunostaining was observed for EGFR in 32.1%, for pEGFR in 21.0%, for PTEN in 38.3%, for pAKT in 5.3%, and for pERK in 4.3% of tumor samples. Positive EGFR immunostaining was associated with squamous cell carcinoma of the cervix (odds ratio [OR], 7.41; 95% confidence interval [CI], 3.38-16.23, P < .001), negative pEGFR immunostaining with poor differentiation (OR, 0.39; 95% CI, 0.20-0.73, P = .004), and negative PTEN immunostaining with metastatic pelvic lymph nodes (OR, 0.51; 95% CI, 0.30-0.90, P = .019). In multivariate analysis, only pelvic lymph node metastasis (hazard ratio, 6.11; 95% CI, 3.46-10.77, P < .001) and poor differentiation (hazard ratio, 1.91; 95% CI, 1.12-3.26, P = .018) were related to disease-specific survival. In early-stage cervical cancer, loss of PTEN expression is associated with pelvic lymph node metastasis, suggesting PTEN to be one of the tumor suppressor genes affecting pelvic lymph node metastasis. However, expression of EGFR pathway components does not appear to have prognostic impact in surgically treated early-stage cervical cancer.
本研究旨在探讨表皮生长因子受体(EGFR)成分的表达与早期宫颈癌临床行为的关系。收集了 336 例连续的国际妇产科联合会(FIGO)分期 IB-IIA 期宫颈癌患者的组织样本,所有患者均接受根治性手术治疗。在标准治疗和随访过程中前瞻性获得临床病理和随访数据。作为 EGFR 通路的代表,采用组织微阵列免疫组化检测 EGFR、pEGFR、PTEN、pAKT 和 pERK 的表达。肿瘤样本中 EGFR 阳性免疫染色率为 32.1%,pEGFR 为 21.0%,PTEN 为 38.3%,pAKT 为 5.3%,pERK 为 4.3%。EGFR 阳性免疫染色与宫颈鳞癌相关(比值比[OR],7.41;95%置信区间[CI],3.38-16.23,P<0.001),pEGFR 阴性免疫染色与分化不良相关(OR,0.39;95%CI,0.20-0.73,P=0.004),PTEN 阴性免疫染色与转移性盆腔淋巴结相关(OR,0.51;95%CI,0.30-0.90,P=0.019)。多因素分析显示,仅盆腔淋巴结转移(风险比,6.11;95%CI,3.46-10.77,P<0.001)和分化不良(风险比,1.91;95%CI,1.12-3.26,P=0.018)与疾病特异性生存相关。在早期宫颈癌中,PTEN 表达缺失与盆腔淋巴结转移相关,提示 PTEN 是影响盆腔淋巴结转移的肿瘤抑制基因之一。然而,EGFR 通路成分的表达在接受手术治疗的早期宫颈癌中似乎没有预后影响。