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Clinical Cancer Research 14, 3291, June 1, 2008. doi: 10.1158/1078-0432.CCR-07-1322
© 2008 American Association for Cancer Research

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Human Cancer Biology

ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer

Thomas John1, Otavia L. Caballero3, Suzanne J. Svobodová2, Alan Kong1, Ramon Chua3, Judy Browning1, Sheila Fortunato3, Siddhartha Deb1, Melinda Hsu3, Craig A. Gedye1, Ian D. Davis1, Nasser Altorki4, Andrew J. Simpson3, Yao-Tseng Chen4, Marilyn Monk5 and Jonathan S. Cebon1

Authors' Affiliations: 1 Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, and 2 Department of Pathology, Austin Health, Heidelberg, Victoria, Australia; 3 Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Centre, and 4 Weill Cornell Medical College, New York, New York; and 5 Institute of Child Health, London, United Kingdom

Requests for reprints: Jonathan Cebon, Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. Phone: 61-3-9496-5462; Fax: 61-3-9457-6698; E-mail: Jonathan.cebon{at}ludwig.edu.au.

Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A (ECSA), later named developmental pluripotency associated-2 (DPPA2), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy.

Experimental Design: ECSA/DPPA2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot.

Results: ECSA/DPPA2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2-positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls.

Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA2 is a promising target for antigen-specific immunotherapy in NSCLC.




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M. Monk, M. Hitchins, and S. Hawes
Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development
Mol. Hum. Reprod., June 1, 2008; 14(6): 347 - 355.
[Abstract] [Full Text] [PDF]




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Copyright © 2008 by the American Association for Cancer Research.