Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer.
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.
Tchabo
Nana E
NE
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Mhawech-Fauceglia
Paulette
P
Caballero
Otavia L
OL
Villella
Jeannine
J
Beck
Amy F
AF
Miliotto
Anthony J
AJ
Liao
Jianqun
J
Andrews
Christopher
C
Lele
Shashikant
S
Old
Lloyd J
LJ
Odunsi
Kunle
K
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
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
Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Apr 18;38(2):124-7
16617350
Nat Rev Cancer. 2005 Aug;5(8):615-25
16034368
Genomics. 2000 Sep 15;68(3):305-12
10995572
Cancer Immun. 2007 Nov 06;7:18
17983203
Cancer Res. 2005 Sep 1;65(17):7751-62
16140943
Clin Cancer Res. 2008 May 1;14(9):2740-8
18451240
Cancer Immun. 2004 Oct 18;4:10
15487888
Cancer Immun. 2007 Dec 21;7:21
18095639
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12837-42
17652518
Cancer Immun. 2004 Jan 23;4:1
14738373
Clin Cancer Res. 2008 Jun 1;14(11):3291-8
18519755
Cancer Immun. 2001 Mar 30;1:1
12747762
Int J Cancer. 2008 May 1;122(9):2038-43
18183594
Cancer Res. 2003 Sep 15;63(18):6076-83
14522938
Nucleic Acids Res. 2009 Jan;37(Database issue):D816-9
18838390
Cancer Immun. 2007 Nov 06;7:19
17983204
Cancer Res. 2007 Oct 1;67(19):9528-34
17909063
Mol Hum Reprod. 2008 Jun;14(6):347-55
18467432