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Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

BACKGROUND: Primary 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. METHODS: Eightee...

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Autores principales: Gatalica, Zoran, Vranic, Semir, Krušlin, Božo, Poorman, Kelsey, Stafford, Phillip, Kacerovska, Denisa, Senarathne, Wijendra, Florento, Elena, Contreras, Elma, Leary, Alexandra, Choi, April, In, Gino K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013075/
https://www.ncbi.nlm.nih.gov/pubmed/31899853
http://dx.doi.org/10.1002/cam4.2820
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author Gatalica, Zoran
Vranic, Semir
Krušlin, Božo
Poorman, Kelsey
Stafford, Phillip
Kacerovska, Denisa
Senarathne, Wijendra
Florento, Elena
Contreras, Elma
Leary, Alexandra
Choi, April
In, Gino K.
author_facet Gatalica, Zoran
Vranic, Semir
Krušlin, Božo
Poorman, Kelsey
Stafford, Phillip
Kacerovska, Denisa
Senarathne, Wijendra
Florento, Elena
Contreras, Elma
Leary, Alexandra
Choi, April
In, Gino K.
author_sort Gatalica, Zoran
collection PubMed
description BACKGROUND: Primary 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-70130752020-03-24 Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease Gatalica, Zoran Vranic, Semir Krušlin, Božo Poorman, Kelsey Stafford, Phillip Kacerovska, Denisa Senarathne, Wijendra Florento, Elena Contreras, Elma Leary, Alexandra Choi, April In, Gino K. Cancer Med Clinical Cancer Research BACKGROUND: Primary 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. John Wiley and Sons Inc. 2020-01-03 /pmc/articles/PMC7013075/ /pubmed/31899853 http://dx.doi.org/10.1002/cam4.2820 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Gatalica, Zoran
Vranic, Semir
Krušlin, Božo
Poorman, Kelsey
Stafford, Phillip
Kacerovska, Denisa
Senarathne, Wijendra
Florento, Elena
Contreras, Elma
Leary, Alexandra
Choi, April
In, Gino K.
Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title_full Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title_fullStr Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title_full_unstemmed Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title_short Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease
title_sort comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary paget's disease
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013075/
https://www.ncbi.nlm.nih.gov/pubmed/31899853
http://dx.doi.org/10.1002/cam4.2820
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