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Imaging, Diagnosis, Prognosis

Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer

G. Larry Maxwell, G.V.R. Chandramouli, Lou Dainty, Tracy J. Litzi, Andrew Berchuck, J. Carl Barrett and John I. Risinger
G. Larry Maxwell
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G.V.R. Chandramouli
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Lou Dainty
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Tracy J. Litzi
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Andrew Berchuck
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J. Carl Barrett
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John I. Risinger
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DOI: 10.1158/1078-0432.CCR-04-2001 Published June 2005
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  • Fig. 1.
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    Fig. 1.

    A, unsupervised analysis using multidimensional scaling based on the overall gene expression in endometrioid (green) and papillary serous (blue) using 1-correlation as distance metric of 18.4 K transcripts detected in at least 50% of the arrays. B, differentially expressed genes between 66 endometrioid carcinomas and 24 papillary serous carcinomas. Twenty-five most up-regulated and 25 most down-regulated genes at P < 0.001. Each sample in the heat map is labeled histology, stage of disease, and coded tumor number. The heat map was color coded using red for up-regulation from normal endometria and green for down-regulation.

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    Fig. 2.

    A, unsupervised analysis using multidimensional scaling based on the overall gene expression in endometrioid carcinomas (red) and mixed mullerian tumor (blue). B, genes differentially expressed between 66 endometrioid carcinomas (E) and 29 mixed mullerian tumors (MMT) of the uterus. Twenty-five most up-regulated and 25 most down-regulated genes at P < 0.001. Each sample in the heat map is labeled histology, stage of disease, and coded tumor number. The heat map was color-coded using red for up-regulation from normal endometria and green for down-regulation.

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    Fig. 3.

    A, unsupervised analysis using multidimensional scaling based on the overall gene expression in mixed mullerian tumor (red) and papillary serous carcinoma (blue). B, list of 25 highest and 25 lowest differentially expressed genes (at least 2-fold) for 29 mixed mullerian tumors and 24 papillary serous (PS) carcinomas (P < 0.001). Each sample in the heat map is labeled histology, stage of disease, and coded tumor number. The heat map was color coded using red for up-regulation from normal endometria and green for down-regulation.

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    Fig. 4.

    Microarray expression and quantitative PCR (TaqMan) expression analysis of six selected genes differentially expressed between mixed mullerian tumors, endometrial carcinoma, and papillary serous carcinoma.

Tables

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  • Table 1. Differentially expressed genes characteristic of endometrioid serous carcinomas

    Differentially expressed genes characteristic of endometrioid serous carcinomas

    E/PSE/MMTUniGeneGeneMapDescription
    8.02719.501Hs.104696KIAA13241p13.3-p13.2Maba1
    6.2795.010Hs.420036GAD12q31Glutamate decarboxylase 1 (brain, 67 kDa)
    5.81919.348Hs.11583816p13.11Homo sapiens cDNA FLJ44282 fis, clone TRACH2003516
    5.7459.057Hs.82961TFF321q22.3Trefoil factor 3 (intestinal)
    5.60316.175Hs.226391AGR27p21.3Anterior gradient 2 homologue (Xenopus laevis)
    4.9898.530Hs.155651FOXA220p11Forkhead box A2
    4.6278.343Hs.48403FLJ1084717p11.2Hypothetical protein FLJ10847
    4.2044.452Hs.46452SCGB2A211q13Secretoglobin, family 2A, member 2
    3.8078.202Hs.24879PPAP2C19p13Phosphatidic acid phosphatase type 2C
    3.7848.290Hs.145807TMC516p13.11Transmembrane channel–like 5
    3.6925.524Hs.104696KIAA13241p13.3-p13.2Maba1
    3.6173.865Hs.99348DLX57q22Distal-less homeo box 5
    3.4067.984Hs.200286DKFZp547I0481p31.1Hypothetical protein DKFZp547I048
    3.2236.239Hs.6168KIAA070316q24.1KIAA0703 gene product
    3.1854.521Hs.158857RASSF64q21.21Ras association (RalGDS/AF-6) domain family 6
    3.1724.746Hs.445072ARGBP24q35.1Arg/Abl-interacting protein ArgBP2
    3.1073.655Hs.89404MSX25q34-q35Msh homeo box homologue 2 (Drosophila)
    2.6334.250Hs.512682CEACAM119q13.2Carcinoembryonic antigen–related cell adhesion molecule 1
    2.5893.198Hs.288240IL20RA6q22.33-q23.1Interleukin 20 receptor α
    2.5728.822Hs.116992HGD3q21-q23Homogentisate 1,2-dioxygenase (homogentisate oxidase)
    2.5472.755Hs.211587PLA2G4A1q25Phospholipase A2, group IVA (cytosolic, calcium-dependent)
    2.4872.187Hs.306278CD4411p13CD44 antigen (homing function and Indian blood group system)
    2.4702.941Hs.1568804Homo sapiens, clone IMAGE:4791597, mRNA
    2.4583.778Hs.5191374Homo sapiens cDNA FLJ37284 fis, clone BRAMY2013590
    2.4564.519Hs.432615Homo sapiens transcribed sequence
    2.4282.310Hs.11713ELF511p13-p12E74-like factor 5 (Ets domain transcription factor)
    2.4203.915Hs.145807TMC516p13.11Transmembrane channel–like 5
    2.3832.065Hs.348802NMA10p12.3-p11.2Putative transmembrane protein
    2.2652.581Hs.306278CD4411p13CD44 antigen (homing function and Indian blood group system)
    2.2188.166Hs.433197ASRGL111q12.3Asparaginase like 1
    2.2152.271Hs.153952NT5E6q14-q215′-Nucleotidase, ecto (CD73)
    2.1842.901Hs.79414PDEF6p21.3Prostate epithelium–specific Ets transcription factor
    2.1243.088Hs.439760CYP4X11p33Likely orthologue of rat cytochrome P450 4X1
    2.1212.453Hs.293685Homo sapiens transcribed sequence
    2.0963.305Hs.518542HGD3q21-q23Homogentisate 1,2-dioxygenase (homogentisate oxidase)
    2.0734.648Hs.194710GCNT315q21.3Glucosaminyl (N-acetyl) transferase 3, mucin type
    0.4850.411Hs.183650CRABP21q21.3Cellular retinoic acid binding protein 2
    0.4790.498Hs.12844EGFL6Xp22EGF-like domain, multiple 6
    0.4720.485Hs.308628SIAT8D5q21Sialyltransferase 8D (-2, 8-polysialyltransferase)
    0.4650.384Hs.298646PRO20008q24.13PRO2000 protein
    0.4540.451Hs.414407HEC18p11.31Highly expressed in cancer, rich in leucine heptad repeats
    0.4500.279Hs.336224TMEFF19q31Transmembrane protein with EGF-like
    0.4440.469Hs.137047FLJ251573p24.2Hypothetical protein FLJ25157
    0.4430.193Hs.76118UCHL14p14Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
    0.4410.426Hs.445098FLJ203541p31.2Hypothetical protein FLJ20354
    0.4370.381Hs.169840TTK6q13-q21TTK protein kinase
    0.4300.364Hs.125124EPHB21p36.1-p35EphB2
    0.4230.349Hs.79440IMP-37p11IGF-II mRNA-binding protein 3
    0.4070.315Hs.250687TRPC13q22-q24Transient receptor potential cation channel, subfamily C
    0.3840.421Hs.444096Human full-length cDNA 5′-end of clone CS0DK007YB08
    0.3820.382Hs.65366KIAA1495Xq24KIAA1495 protein
    0.3700.435Hs.132246SLC38A112q13.11Solute carrier family 38, member 1
    0.3580.311Hs.444096Human full-length cDNA 5′-end of clone CS0DK007YB08
    0.3460.264Hs.512414NR3C15q31Nuclear receptor subfamily 3C1 (glucocorticoid receptor)
    0.3370.322Hs.30299IMP-23q28IGF-II mRNA-binding protein 2
    0.3080.199Hs.43577ATP8B21q22ATPase, class I, type 8B, member 2
    0.3060.298Hs.444096Human full-length cDNA 5′-end of clone CS0DK007YB08
    0.3020.135Hs.126085LRRN13p26.2Leucine-rich repeat neuronal 1
    0.2760.210Hs.14968PLAG18q12Pleiomorphic adenoma gene 1
    0.2590.104Hs.349109IGF211p15.5Insulin-like growth factor 2 (somatomedin A)
    2.0422.679Hs.387367CYP39A16p21.1-p11.2Cytochrome P450, family 39, subfamily A, polypeptide 1
    2.0353.538Hs.184510SFN1p35.3Stratifin
    2.0312.162Hs.302738SLC26A25q31-q34Solute carrier family 26 (sulfate transporter), member 2
    2.0312.372Hs.105547NPDC19q34.3Neural proliferation, differentiation and control, 1
    2.0303.485Hs.28491SATXp22.1Spermidine/spermine N1-acetyltransferase
    2.0172.669Hs.302738SLC26A25q31-q34Solute carrier family 26 (sulfate transporter), member 2
    • Abbreviations: E, endometrioid carcinoma; PS, papillary serous carcinoma; MMT, mixed mullerian tumors.

  • Table 2. Differentially expressed genes characteristic of papillary serous carcinoma

    Differentially expressed genes characteristics of papillary serous carcinoma

    PS/EPS/MMTGeneUniGeneMapDescription
    7.1279.804VGLL1Hs.9030Xq26.3Vestigial like 1 (Drosophila)
    4.8608.945Hs.147613Homo sapiens transcribed sequences
    4.2927.194Hs.372225Homo sapiens transcribed sequences
    3.7573.366NPR1Hs.4388641q21-q22Natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)
    3.2543.357LOC221002Hs.12529310q11.21CG4853 gene product
    3.1872.580FAM20AHs.14463317q24.3Family with sequence similarity 20, member A
    3.1132.533ESTs, weakly similar to JC5314 CDC28/cdc2-like kinase associating arginine-serine cyclophilin
    2.8543.476WNT7AHs.722903p25Wingless-type mouse mammary tumor virus integration site family, member 7A
    2.7893.011THRBHs.2032133p24.3Thyroid hormone receptor β [erythroblastic leukemia viral (v-erb-a) oncogene homologue 2, avian]
    2.5452.704Hs.391828Homo sapiens transcribed sequence with moderate similarity to protein NP_060265.1
    2.3793.736PTGS1Hs.884749q32-q33.3Prostaglandin endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)
    2.3632.013LUHs.15504819q13.2Lutheran blood group (Auberger B antigen included)
    2.3152.977PTGS1Hs.884749q32-q33.3Prostaglandin endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)
    2.2772.748PTGS1Hs.884749q32-q33.3Prostaglandin endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)
    2.2552.010CDH6Hs.329635p15.1-p14Cadherin 6, type 2, K-cadherin (fetal kidney)
    2.2403.697Hs.20144113Homo sapiens cDNA FLJ11076 fis, clone PLACE1005077.
    2.1873.340HUMPPAHs.7835817q25.2Paraneoplastic antigen
    2.1782.477KIAA1554Hs.19564217q25.3KIAA1554 protein
    2.0972.479Hs.152422Homo sapiens cDNA FLJ27210 fis, clone SYN03494
    2.0232.317Hs.124776Homo sapiens mRNA; cDNA DKFZp564N1116 (from clone DKFZp564N1116)
    0.4800.396FGFR1Hs.7488p11.2-p11.1Fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)
    0.4490.468KIAA1025Hs.43524912q24.22KIAA1025 protein
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Clinical Cancer Research: 11 (11)
June 2005
Volume 11, Issue 11
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Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer
G. Larry Maxwell, G.V.R. Chandramouli, Lou Dainty, Tracy J. Litzi, Andrew Berchuck, J. Carl Barrett and John I. Risinger
Clin Cancer Res June 1 2005 (11) (11) 4056-4066; DOI: 10.1158/1078-0432.CCR-04-2001

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Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer
G. Larry Maxwell, G.V.R. Chandramouli, Lou Dainty, Tracy J. Litzi, Andrew Berchuck, J. Carl Barrett and John I. Risinger
Clin Cancer Res June 1 2005 (11) (11) 4056-4066; DOI: 10.1158/1078-0432.CCR-04-2001
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