Research Centre of the University of Montreal Hospital Centre/Montreal Cancer Institute, Montreal, QC, Canada.
Int J Oncol. 2013 Mar;42(3):912-20. doi: 10.3892/ijo.2013.1797. Epub 2013 Jan 23.
The frequent loss of chromosome 17 in epithelial ovarian carcinomas (EOC), particularly high-grade serous carcinomas (HGSC), has been attributed to the disruption of TP53 (at 17p13.1) and other chromosome 17 genes suspected to play a role in tumour suppressor pathways. In a transcriptome analysis of HGSC, we showed underexpression of a number of chromosome 17 genes, which included FKBP10 (at 17q21.1) and collagen I α 1 (COL1A1; at 17q21.33). FKBP10 codes for the immunophilin FKBP65 and is suspected to act as a chaperone for COL1A1. We have investigated FKBP10 (gene) and FKBP65 (protein) expression in HGSC samples and EOC cell lines that differ in their tumourigenic potential. COL1A1 expression was also investigated given the purported function of FKBP65. RT-PCR analysis verified underexpression of FKBP10 and COL1A1 in HGSCs (n=14) and six tumourigenic EOC cell lines, relative to normal ovarian surface epithelial cells and a non-tumourigenic EOC cell line. Immunohistochemistry analyses of 196 HGSC samples using tissue microarrays revealed variable staining intensities in the epithelial tumour component where only 7.8% and 1.0% of samples stained intensely for FKBP65 and COL1A1, respectively. Variable staining intensities were also observed for the stromal component where 23.6% and 24.1% stained intensely for FKBP65 and COL1A1, respectively. There was no significant correlation of staining intensity of either protein with disease stage. Staining of FKBP65 was clearly visible in normal epithelial cells of the ovarian surface and fallopian tube. There was a significant correlation between absence of FKBP65 staining in the epithelial cell component of the tumour and prolonged overall survival (p<0.001). Our results suggest that underexpression of FKBP65 protein is characteristic of HGSCs and that this expression profile may be linked to molecular pathways associated with an unfavourable outcome in cancer patients.
在卵巢上皮性癌（EOC）中，尤其是高级别浆液性癌（HGSC）中，染色体 17 的频繁缺失归因于 TP53（位于 17p13.1）和其他染色体 17 基因的破坏，这些基因被怀疑在肿瘤抑制途径中发挥作用。在 HGSC 的转录组分析中，我们显示出许多染色体 17 基因的表达下调，其中包括 FKBP10（位于 17q21.1）和胶原蛋白 Iα1（COL1A1；位于 17q21.33）。FKBP10 编码免疫亲和素 FKBP65，被怀疑作为 COL1A1 的伴侣蛋白发挥作用。我们已经研究了 HGSC 样本和在肿瘤发生潜力方面不同的 EOC 细胞系中 FKBP10（基因）和 FKBP65（蛋白）的表达。鉴于 FKBP65 的假定功能，还研究了 COL1A1 的表达。RT-PCR 分析证实，与正常卵巢表面上皮细胞和非肿瘤性 EOC 细胞系相比，HGSC（n=14）和六种肿瘤发生 EOC 细胞系中 FKBP10 和 COL1A1 的表达下调。使用组织微阵列对 196 例 HGSC 样本进行免疫组织化学分析显示，上皮肿瘤成分中的染色强度存在差异，其中仅 7.8%和 1.0%的样本分别对 FKBP65 和 COL1A1 进行强烈染色。基质成分的染色强度也存在差异，其中 23.6%和 24.1%的样本分别对 FKBP65 和 COL1A1 进行强烈染色。两种蛋白的染色强度与疾病阶段均无显著相关性。FKBP65 在卵巢表面和输卵管的正常上皮细胞中清晰可见染色。肿瘤上皮细胞成分中 FKBP65 染色缺失与总生存期延长显著相关（p<0.001）。我们的结果表明，FKBP65 蛋白的表达下调是 HGSC 的特征，并且这种表达谱可能与与癌症患者不良预后相关的分子途径有关。
