Engelstaedter Verena, Boda Judith, Völklein Christine, Engel Jutta, Jeschke Udo, Kirchner Thomas, Mayr Doris
Department of Obstetrics and Gynecology, Campus Innenstadt;
Exp Ther Med. 2012 May;3(5):828-834. doi: 10.3892/etm.2012.481. Epub 2012 Feb 13.
Patients with advanced ovarian cancer (FIGO stage III) have a poor clinical prognosis. However, these patients show distinct differences in their survival time, possibly due to differing responses to chemotherapy and differing tumor biology. In contrast to histological subtype, grading and staging, which are known to affect a patient's prognosis, the impact of the human epidermal growth factor receptor 2 (Her-2/neu), topoisomerase IIα and epidermal growth factor receptor (EGFR) on survival remain inconclusive. Therefore, the aim of this study was to assess their impact on survival in a group of advanced ovarian cancer patients. Tissue microarrays were constructed from specimens of 243 patients. Gene copy and chromosome numbers were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Scoring for the latter was calculated by considering the percentage of positive tumor cells and the relative staining intensity. FISH results were evaluated by previously published recommendations and correlated with overall survival. Using IHC, 1.6% of the cases that were tested for Her-2/neu and topoisomerase IIα were strongly positive, and 12.3% were positive for EGFR. Using FISH, 4.4% amplifications and 2.1% polysomies for Her-2/neu were identified; topoisomerase IIα showed 2.2% amplifications, 0.4% deletions and 3.5% polysomies. We observed 10.8% high polysomies, but no amplification for EGFR. None of the results obtained by IHC or FISH correlated with overall survival. In general, Her-2/neu, topoisomerase IIα and EGFR may be prognostic factors in ovarian carcinomas. However, within this group of FIGO stage III patients, differences in gene aberration or protein expression were not able to predict differences in survival.
晚期卵巢癌(国际妇产科联盟[FIGO]分期为III期)患者的临床预后较差。然而,这些患者的生存时间存在明显差异,这可能是由于对化疗的反应不同以及肿瘤生物学特性不同所致。与已知会影响患者预后的组织学亚型、分级和分期不同,人表皮生长因子受体2(Her-2/neu)、拓扑异构酶IIα和表皮生长因子受体(EGFR)对生存的影响尚无定论。因此,本研究的目的是评估它们对一组晚期卵巢癌患者生存的影响。从243例患者的标本构建组织微阵列。通过荧光原位杂交(FISH)评估基因拷贝数和染色体数目,通过免疫组织化学(IHC)评估蛋白质表达。后者的评分通过考虑阳性肿瘤细胞的百分比和相对染色强度来计算。FISH结果根据先前发表的建议进行评估,并与总生存相关。使用IHC检测,检测Her-2/neu和拓扑异构酶IIα的病例中1.6%为强阳性,12.3%为EGFR阳性。使用FISH检测,发现Her-2/neu有4.4%扩增和2.1%多体性;拓扑异构酶IIα显示2.2%扩增、0.4%缺失和3.5%多体性。我们观察到EGFR有10.8%的高多体性,但无扩增。IHC或FISH获得的结果均与总生存无关。总体而言,Her-2/neu、拓扑异构酶IIα和EGFR可能是卵巢癌的预后因素。然而,在这组FIGO III期患者中,基因畸变或蛋白质表达的差异无法预测生存差异。