Esteller M, García A, Martínez i Palones J M, Cabero A, Reventós J
Unitat de Recerca Biomèdica, Hospital Universitari Materno-Infantil Vall d'Hebrón, Barcelona, Spain.
Cancer. 1995 Apr 15;75(8):2139-46. doi: 10.1002/1097-0142(19950415)75:8<2139::aid-cncr2820750817>3.0.co;2-6.
It currently is well established that the activation of protooncogenes could trigger uncontrolled cell growth and cancer development. Although this correlation already has been evidenced in several human tumors, no conclusive studies have related oncogene activation with the development of endometrial neoplasia. Nevertheless, few reports suggest that c-erbB-2/neu, which is a prognostic marker in breast cancer, epidermal growth factor receptor (EGFR), which is overexpressed in a variety of neoplasms, and fibroblast growth factor-3 (FGF-3/INT-2), which has been found to be amplified in breast and ovarian cancer, could be implicated in the development of endometrial adenocarcinoma.
Amplification of c-erbB-2/neu, EGFR, and FGF-3/INT-2 was examined in 50 endometrial carcinomas, 10 adenomatous hyperplasias, and 50 normal endometrial samples, using the genomic differential polymerase chain reaction with the single copy reference gene interferon-gamma. Quantitation of the ratios between the amplified bands was assessed by image analysis.
c-erbB-2 and FGF-3/INT-2 were amplified in a first group of 7 (14%) and a further group of 7 (14%) patients, respectively, of a total of 50 in whom endometrial cancer had been studied. In the latter seven, a strong correlation between this genetic marker and an advanced disease stage (International Federation of Gynecology and Obstetrics Stage III) was found. In two patients, both genes were amplified. No EGFR gene amplification was detected in any case.
c-erbB-2/neu but not EGFR gene amplification was detected and FGF-3/INT-2 amplification and advanced disease were correlated in endometrial cancer.
目前已明确原癌基因的激活可引发细胞的失控性生长及癌症发展。尽管这种关联已在多种人类肿瘤中得到证实,但尚无确凿研究表明癌基因激活与子宫内膜肿瘤的发生有关。然而,有少数报告指出,在乳腺癌中作为预后标志物的c-erbB-2/neu、在多种肿瘤中过度表达的表皮生长因子受体(EGFR)以及在乳腺癌和卵巢癌中被发现存在扩增的成纤维细胞生长因子-3(FGF-3/INT-2)可能与子宫内膜腺癌的发生有关。
采用以单拷贝参照基因γ干扰素进行基因组差异聚合酶链反应,对50例子宫内膜癌、10例腺瘤样增生以及50例正常子宫内膜样本中的c-erbB-2/neu、EGFR和FGF-3/INT-2进行扩增检测。通过图像分析评估扩增条带之间的比率定量。
在总共50例研究子宫内膜癌的患者中,分别有7例(14%)和另外7例(14%)患者的c-erbB-2和FGF-3/INT-2出现扩增。在后者这7例患者中,发现该遗传标志物与晚期疾病阶段(国际妇产科联盟III期)之间存在强相关性。在2例患者中,两个基因均出现扩增。在任何情况下均未检测到EGFR基因扩增。
在子宫内膜癌中检测到c-erbB-2/neu而非EGFR基因扩增,且FGF-3/INT-2扩增与晚期疾病相关。