title: Proteomic analysis of stage I endometrial cancer tissue: identification of proteins associated with oxidative processes and inflammation.
abstract: OBJECTIVE
  The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.
  
  
  METHODS
  A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins.
  
  
  RESULTS
  209 differentially expressed proteins were identified in a comparison of stage I endometrial cancers and normal post-menopausal endometrium controls (Q<0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q=0.008 and Q=0.00002 respectively).
  
  
  CONCLUSIONS
  These data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.
authors: Division of Gynecologic Oncology, Walter Reed Army Medical Center, 6900 Georgia Avenue, Washington DC 20307, USA. george.maxwell@us.army.mil
authors: G Larry
authors: GL
authors: Maxwell
authors: Brian L
authors: BL
authors: Hood
authors: Roger
authors: R
authors: Day
authors: Uma
authors: U
authors: Chandran
authors: David
authors: D
authors: Kirchner
authors: V S Kumar
authors: VS
authors: Kolli
authors: Nicolas W
authors: NW
authors: Bateman
authors: Jay
authors: J
authors: Allard
authors: Caela
authors: C
authors: Miller
authors: Mai
authors: M
authors: Sun
authors: Melanie S
authors: MS
authors: Flint
authors: Chris
authors: C
authors: Zahn
authors: Julie
authors: J
authors: Oliver
authors: Subhadra
authors: S
authors: Banerjee
authors: Tracy
authors: T
authors: Litzi
authors: Anil
authors: A
authors: Parwani
authors: Glenn
authors: G
authors: Sandburg
authors: Scott
authors: S
authors: Rose
authors: Michael J
authors: MJ
authors: Becich
authors: Andrew
authors: A
authors: Berchuck
authors: Elise
authors: E
authors: Kohn
authors: John I
authors: JI
authors: Risinger
authors: Thomas P
authors: TP
authors: Conrads
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D009367:Neoplasm Staging; D017698:Postmenopause / Q000378:metabolism; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D009363:Neoplasm Proteins