FKBP10/FKBP65 expression in high-grade ovarian serous carcinoma and             its association with patient outcome.
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.
Research Centre of the University of Montreal Hospital Centre/Montreal                     Cancer Institute, Montreal, QC, Canada.
Michael C J
MC
Quinn
Paulina M
PM
Wojnarowicz
Amy
A
Pickett
Diane M
DM
Provencher
Anne-Marie
AM
Mes-Masson
Elaine C
EC
Davis
Patricia N
PN
Tonin
D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D024042:Collagen Type I / Q000096:biosynthesis*; D000090602:Collagen Type I, alpha 1 Chain; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D058496:Smith-Magenis Syndrome; D013534:Survival; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human