title: Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer.
abstract: Cancer-embryo antigens or developmentally restricted differentiation antigens (DRDAGs), such as PLAC1 (CT92) and developmental pluripotency associated-2 (DPPA2/CT100), are expressed in pluripotent embryonic cells. They are also recognized as cancer-testis antigens (CT) which are proteins normally expressed only in the human germ line but that are also present in a significant subset of malignant tumors. These antigens may prove to be markers of 'repopulating' cells with stem cell-like characteristics and could be critical targets for immunotherapy in epithelial ovarian cancer (EOC). Our objective was to define the frequency of expression and immunogenicity of PLAC1 and DPPA2 in EOC and correlate expression with clinical outcome. One-step reverse transcriptase PCR was performed on 101 EOC samples and a panel of normal tissues. Expression of PLAC1 and DPPA2 in the EOC specimens was 21/101 (21%) and 31/101 (31%) respectively. In normal tissues, PLAC1 expression was restricted to the placenta while DPPA2 expression was restricted to the placenta and testis. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were also performed on a subset of specimens. Humoral immunity was demonstrable in 2/12 serum samples from patients whose tumors expressed DPPA2. There was no demonstrable antibody response to PLAC1 in patients with PLAC1 positive tumors. The presence of PLAC1 and DPPA2 did not have a statistically significant effect on recurrence-free and overall survival. The tissue-restricted expression of PLAC1 and DPPA2, their expression in a significant proportion of EOC patients, and their potential to represent markers of stem cells make DRDAGs attractive targets for antigen-specific immunotherapy in EOC.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Nana E
authors.initials: NE
authors.lastname: Tchabo
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.forename: Otavia L
authors.initials: OL
authors.lastname: Caballero
authors.forename: Jeannine
authors.initials: J
authors.lastname: Villella
authors.forename: Amy F
authors.initials: AF
authors.lastname: Beck
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Miliotto
authors.forename: Jianqun
authors.initials: J
authors.lastname: Liao
authors.forename: Christopher
authors.initials: C
authors.lastname: Andrews
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D018797:Cell Cycle Proteins; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011257:Pregnancy Proteins / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D014157:Transcription Factors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C502836:DPPA2 protein, human; D009687:Nuclear Proteins; C415583:PLAC1 protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D014157:Transcription Factors
references.citation: Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Apr 18;38(2):124-7
references.pmid: 16617350
references.citation: Nat Rev Cancer. 2005 Aug;5(8):615-25
references.pmid: 16034368
references.citation: Genomics. 2000 Sep 15;68(3):305-12
references.pmid: 10995572
references.citation: Cancer Immun. 2007 Nov 06;7:18
references.pmid: 17983203
references.citation: Cancer Res. 2005 Sep 1;65(17):7751-62
references.pmid: 16140943
references.citation: Clin Cancer Res. 2008 May 1;14(9):2740-8
references.pmid: 18451240
references.citation: Cancer Immun. 2004 Oct 18;4:10
references.pmid: 15487888
references.citation: Cancer Immun. 2007 Dec 21;7:21
references.pmid: 18095639
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12837-42
references.pmid: 17652518
references.citation: Cancer Immun. 2004 Jan 23;4:1
references.pmid: 14738373
references.citation: Clin Cancer Res. 2008 Jun 1;14(11):3291-8
references.pmid: 18519755
references.citation: Cancer Immun. 2001 Mar 30;1:1
references.pmid: 12747762
references.citation: Int J Cancer. 2008 May 1;122(9):2038-43
references.pmid: 18183594
references.citation: Cancer Res. 2003 Sep 15;63(18):6076-83
references.pmid: 14522938
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D816-9
references.pmid: 18838390
references.citation: Cancer Immun. 2007 Nov 06;7:19
references.pmid: 17983204
references.citation: Cancer Res. 2007 Oct 1;67(19):9528-34
references.pmid: 17909063
references.citation: Mol Hum Reprod. 2008 Jun;14(6):347-55
references.pmid: 18467432