Gene expression signatures differentiate ovarian/peritoneal  serous carcinoma from breast carcinoma in effusions.
Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities.With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies,as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina.Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3,PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery.
Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. bend@medisin.uio.no
Ben
B
Davidson
Helene Tuft
HT
Stavnes
Arild
A
Holth
Xu
X
Chen
Yanqin
Y
Yang
Ie-Ming
IeM
Shih
Tian-Li
TL
Wang
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D010455:Peptides; C051838:TFF1 protein, human; C082495:TFF3 protein, human; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII