Siegfried S, Pekonen F, Nyman T, Ammälä M, Rutanen E M
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Cancer. 1997 Mar 15;79(6):1166-71. doi: 10.1002/(sici)1097-0142(19970315)79:6<1166::aid-cncr15>3.0.co;2-y.
Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is a stromally derived, paracrine growth factor specifically mitogenic for a variety of epithelial cells. The KGF receptor (KGFR), which is a splice variant of the FGF receptor-2 (FGFR-2)/bek gene, is expressed only in epithelial cells. In this study, the expression of mRNAs encoding KGF, KGFR, and FGFR-2 in endometrial adenocarcinoma and in carcinosarcoma tissues was examined and the expression of the same mRNAs was compared with cycling endometrium.
Specimens of tumor tissue were collected from 14 women with well differentiated endometrial adenocarcinoma and from 4 women with carcinosarcoma. All samples were obtained at the primary surgery before any treatment was initiated. In addition, endometrial tissues from 19 premenopausal women with normal menstrual cycles were examined. The expression of specific mRNAs in the endometrial samples was assessed using quantitative reverse transcriptase polymerase chain reaction. The results were analyzed by the nonparametric Kruskal-Wallis statistic.
The KGF mRNA expression was significantly lower in endometrial adenocarcinoma tissue compared with cycling endometrial tissues, whereas no difference was found between carcinosarcoma tissue and cycling endometrium. The relative level of KGFR mRNA in endometrial adenocarcinoma did not differ from that in cycling endometrium, but was significantly higher compared with carcinosarcomas. No differences were observed in FGFR-2 mRNA expression between cycling endometrium and tumor tissues.
To the authors' knowledge, this study demonstrates for the first time the expression of KGF, KGFR, and FGFR-2 mRNAs in endometrial adenocarcinoma and in carcinosarcoma tissues. The relative level of KGF mRNA expression in adenocarcinoma tissue is decreased compared with that in cycling endometrium. The change in epithelial/stromal cell prominence between cycling endometrium and adenocarcinoma tissue may account for the difference in KGF expression but does not explain why KGF receptor expression in same tissues remains unchanged. The impact of altered KGF expression for endometrial tumorigenesis is still unknown.
角质形成细胞生长因子(KGF)是成纤维细胞生长因子(FGF)家族的一员。KGF是一种由基质产生的旁分泌生长因子,对多种上皮细胞具有特异性促有丝分裂作用。KGF受体(KGFR)是FGF受体-2(FGFR-2)/bek基因的剪接变体,仅在上皮细胞中表达。在本研究中,检测了子宫内膜腺癌和癌肉瘤组织中编码KGF、KGFR和FGFR-2的mRNA的表达,并将相同mRNA的表达与周期性子宫内膜进行了比较。
收集了14例高分化子宫内膜腺癌女性和4例癌肉瘤女性的肿瘤组织标本。所有样本均在初次手术时、未开始任何治疗前获取。此外,还检查了19例月经周期正常的绝经前女性的子宫内膜组织。使用定量逆转录聚合酶链反应评估子宫内膜样本中特定mRNA的表达。结果采用非参数Kruskal-Wallis统计分析。
与周期性子宫内膜组织相比,子宫内膜腺癌组织中KGF mRNA表达显著降低,而癌肉瘤组织与周期性子宫内膜之间未发现差异。子宫内膜腺癌中KGFR mRNA的相对水平与周期性子宫内膜无差异,但与癌肉瘤相比显著更高。周期性子宫内膜与肿瘤组织之间FGFR-2 mRNA表达未观察到差异。
据作者所知,本研究首次证明了KGF、KGFR和FGFR-2 mRNA在子宫内膜腺癌和癌肉瘤组织中的表达。腺癌组织中KGF mRNA表达的相对水平与周期性子宫内膜相比降低。周期性子宫内膜与腺癌组织之间上皮/基质细胞突出度的变化可能解释了KGF表达的差异,但无法解释为何相同组织中KGF受体表达保持不变。KGF表达改变对子宫内膜肿瘤发生的影响仍不清楚。