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Comparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget's disease.
Cancer Medicine ( IF 2.9 ) Pub Date : 2020-01-03 , DOI: 10.1002/cam4.2820 Zoran Gatalica 1 , Semir Vranic 2 , Božo Krušlin 3, 4 , Kelsey Poorman 1 , Phillip Stafford 1 , Denisa Kacerovska 5, 6 , Wijendra Senarathne 1 , Elena Florento 1 , Elma Contreras 1 , Alexandra Leary 7 , April Choi 8 , Gino K In 8
Cancer Medicine ( IF 2.9 ) Pub Date : 2020-01-03 , DOI: 10.1002/cam4.2820 Zoran Gatalica 1 , Semir Vranic 2 , Božo Krušlin 3, 4 , Kelsey Poorman 1 , Phillip Stafford 1 , Denisa Kacerovska 5, 6 , Wijendra Senarathne 1 , Elena Florento 1 , Elma Contreras 1 , Alexandra Leary 7 , April Choi 8 , Gino K In 8
Affiliation
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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.
中文翻译：
原发性乳腺外和乳腺Paget病靶向治疗的生物标志物比较。
背景技术原发性乳腺佩吉特氏病（EMPD）是一种非常罕见的影响肛门生殖器或腋窝区域的皮肤腺癌。它的特点是病程延长，复发，最终转移灶扩散，尚无特效疗法。方法全面分析了18例EMPD（13例外阴和5例阴囊）和10例乳腺Paget病（MPD）的基因突变，融合和拷贝数变化，以及与治疗相关的蛋白质生物标记物。结果TP53和PIK3CA突变在两个队列中均最常见：EMPD中为7/15和5/15。MPD中的1/6和4/7在4/18 EMPD（3个外阴和1个阴囊病例）中检测到HER2基因扩增，而MPD在多数（7/8）例中检测到。在2/12 EMPD和1/6 MPD中观察到TOP2A基因扩增，分别。同样，在EMPD（4/15）和MPD（3/10）之间未观察到雌激素受体表达的差异。两组（12/16 EMPD）和（7/8 MPD）的大多数中也表达了雄激素受体。在1/7 EMPD和1/4 MPD病例中分别检测到ARv7剪接变体。仅在三个外阴EMPD中观察到免疫细胞上的PD-L1表达。与MPD相比，六个EMPD具有“高”的肿瘤突变负担（≥10个突变/ Mb）。来自两个队列的所有测试病例都是MSI稳定的。结论EMPD与其乳腺对应物共享一些可靶向的生物标志物（类固醇受体，PIK3CA信号传导途径，TOP2A扩增）。EMPD中HER2阳性显着降低，而在某些EMPD中观察到免疫检查点抑制剂（高TMB和PD-L1）的生物标志物。
更新日期：2020-01-04
中文翻译：
原发性乳腺外和乳腺Paget病靶向治疗的生物标志物比较。
背景技术原发性乳腺佩吉特氏病（EMPD）是一种非常罕见的影响肛门生殖器或腋窝区域的皮肤腺癌。它的特点是病程延长，复发，最终转移灶扩散，尚无特效疗法。方法全面分析了18例EMPD（13例外阴和5例阴囊）和10例乳腺Paget病（MPD）的基因突变，融合和拷贝数变化，以及与治疗相关的蛋白质生物标记物。结果TP53和PIK3CA突变在两个队列中均最常见：EMPD中为7/15和5/15。MPD中的1/6和4/7在4/18 EMPD（3个外阴和1个阴囊病例）中检测到HER2基因扩增，而MPD在多数（7/8）例中检测到。在2/12 EMPD和1/6 MPD中观察到TOP2A基因扩增，分别。同样，在EMPD（4/15）和MPD（3/10）之间未观察到雌激素受体表达的差异。两组（12/16 EMPD）和（7/8 MPD）的大多数中也表达了雄激素受体。在1/7 EMPD和1/4 MPD病例中分别检测到ARv7剪接变体。仅在三个外阴EMPD中观察到免疫细胞上的PD-L1表达。与MPD相比，六个EMPD具有“高”的肿瘤突变负担（≥10个突变/ Mb）。来自两个队列的所有测试病例都是MSI稳定的。结论EMPD与其乳腺对应物共享一些可靶向的生物标志物（类固醇受体，PIK3CA信号传导途径，TOP2A扩增）。EMPD中HER2阳性显着降低，而在某些EMPD中观察到免疫检查点抑制剂（高TMB和PD-L1）的生物标志物。
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