title: Expression profiles of carcinosarcoma of the uterine corpus-are these similar to carcinoma or sarcoma?
abstract: Uterine carcinosarcoma (CS) is usually classified as uterine endometrial carcinoma (EC). However, CS is more aggressive even compared with high grade EC. CS is also reported to undergo epithelial to mesenchymal transition (EMT). In this study, we compared the gene expression profiles of CS, EC, and uterine sarcoma (US) and evaluated the role of EMT and chromosomal aberrations in CS tumor formation. Frozen tissues of 46 patients (14 CS, 24 EC, and 8 US) were included. The similarity was examined by Gene Set Enrichment Analysis (GSEA), Fisher's exact test, and clustering using "intrinsic gene set". We examined the expression of 39 EMT-related genes and evaluated TGF-beta signaling by phospho-SMAD2/3 (p-SMAD2/3) staining. Chromosomal regions differing between CS and EC were identified by chromosomal GSEA and comparative genomic hybridization (CGH) microarrays. Three statistical methods confirmed that CS resembled US rather than EC. Acquired markers of EMT were upregulated and attenuated markers of EMT were downregulated in CS. Immunohistochemistry showed that carcinomatous region of CS have higher expression of p-SMAD2/3 than EC (P = 0.008). Chromosomal GSEA showed that genes located at 19q13 had higher expression in CS. Furthermore, CGH microarray indicated that the TGFB1 locus at 19q13.1 was amplified in 4 of 7 samples. Based on the expression profile, CS resembles US rather than EC. TGF-beta signaling is activated in CS and chromosomal gains at 19q13, which includes the TGFB1 locus, suggest that this may contribute to high expression of TGF-beta and thereby EMT phenotype of CS.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Chiyoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Fumio
authors.initials: F
authors.lastname: Kataoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Sadako
authors.initials: S
authors.lastname: Nishimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D010750:Phosphoproteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1