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المؤلفGatalica, Zoran
المؤلفVranic, Semir
المؤلفKrušlin, Božo
المؤلفPoorman, Kelsey
المؤلفStafford, Phillip
المؤلفKacerovska, Denisa
المؤلفSenarathne, Wijendra
المؤلفFlorento, Elena
المؤلفContreras, Elma
المؤلفLeary, Alexandra
المؤلفChoi, April
المؤلفIn, Gino K
تاريخ الإتاحة2020-01-05T04:59:44Z
تاريخ النشر2020-01-03
اسم المنشورCancer Medicine
المعرّفhttp://dx.doi.org/10.1002/cam4.2820
الاقتباسGatalica Z, Vranic S, Krušlin B, et al. Comparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget's disease. Cancer Med. 2020;00:1–10. https:// doi.org/10.1002/cam4.2820
معرّف المصادر الموحدhttp://hdl.handle.net/10576/12483
الملخصPrimary Extra-mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy-relevant protein biomarkers). Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD-L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a "high" tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD-L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.
اللغةen
الناشرWiley Open Access
الموضوعextra-mammary Paget's disease
immune therapy
molecular profiling
targeted therapy
العنوانComparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget's disease.
النوعArticle
ESSN2045-7634
dc.accessType Open Access


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