Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A Journal Article

   

Authors:	Pourmaleki, M.; Young, J. H.; Socci, N. D.; Chiang, S.; Edelweiss, M.; Li, Y.; Zhang, M.; Roshal, L.; Chi, D. S.; Busam, K. J.; Mellinghoff, I. K.; Hollmann, T. J.
Article Title:	Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A
Abstract:	Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma of the anogenital region most commonly treated with surgical excision. Surgical margin clearance is often problematic and recurrence rates remain high indicating the need for additional therapeutic options. Topical immunomodulators have been used with reported success suggesting EMPD may respond to other immunotherapies. This study investigates EMPD protein expression of targetable B7 family members and cancer/testis antigens (CTAs) B7-H3, B7-H4, PD-L1, PD-L2, MAGE-A, and NY-ESO-1 and components of antigen presenting machinery B2M and MHC-I. Fifty-seven specimens from 48 patients (31 female and 17 male), representing in situ, invasive, and metastatic disease of primary and secondary origin were stained and scored (627 total slides). The percentage of cases expressing each immune regulatory molecule in the in situ followed by invasive tumor components was: B7-H3 (94, 90), B7-H4 (82, 78), PD-L1 (6, 10), MAGE-A (39, 50), NY-ESO-1 (16, 20), B2M (100, 89), and MHC-I (78, 79). PD-L2 was negative in all cases. There was high correlation between marker expression within the in situ and invasive tumor components of the same case. B7-H4 was preferentially expressed in primary cutaneous EMPD. Co-expression of B7 family members B7-H3 and B7-H4 was found within the in situ and invasive tumor components of 74% and 48% of cases, respectively. These findings provide an initial characterization of EMPD tumor cell expression of B7-H3, B7-H4, PD-L1, PD-L2, MAGE-A, and NY-ESO-1 and indicate the potential for new immunotherapeutic options for patients with EMPD. © 2019 Impact Journals LLC. All rights reserved.
Keywords:	immunohistochemistry; adult; clinical article; human tissue; protein expression; aged; unclassified drug; human cell; cancer incidence; tumor associated leukocyte; metastasis; skin tumor; immunotherapy; cancer testis antigen; ny eso 1 antigen; tumor cell; melanoma antigen; disease duration; cytokeratin 7; tumor classification; cancer/testis antigens; apc protein; programmed death 1 ligand 1; antigen retrieval; oncological parameters; paget skin disease; b7 family; very elderly; human; male; female; article; programmed death 1 ligand 2; cd276 antigen; hierarchical clustering; v set domain containing t cell activation inhibitor 1; extramammary paget disease; targetable molecules
Journal Title:	Oncotarget
Volume:	10
Issue:	58
ISSN:	1949-2553
Publisher:	Impact Journals
Date Published:	2019-10-22
Start Page:	6152
End Page:	6167
Language:	English
PROVIDER:	scopus
PMCID:	PMC6817453
PUBMED:	31692889
DOI:	10.18632/oncotarget.27247
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075710930&partnerID=40&md5=6648fa8b753adfe45603001fbee06565
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/157629