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
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Maryam Pourmaleki1, Jonathan H. Young2,*, Nicholas D. Socci3, Sarah Chiang2, Marcia Edelweiss2, Yanyun Li2, Mianlei Zhang2, Lev Roshal2, Dennis S. Chi4, Klaus J. Busam2, Ingo K. Mellinghoff1,5 and Travis J. Hollmann2
1 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
2 Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
3 Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4 Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
5 Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
* Present address: School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
|Travis J. Hollmann,||email:||[email protected]|
Keywords: extramammary paget disease; B7 family; cancer/testis antigens; targetable molecules; immunotherapy
Received: June 10, 2019 Accepted: September 16, 2019 Published: October 22, 2019
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.
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