Biomarkers

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Identification of a rare MET variant in a familial case of extramammary Paget’s disease

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Identification of a rare MET variant in a familial case of extramammary Paget’s disease

Extramammary Paget’s disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in elderly individuals. A limited number of paired familial EMPD cases (i.e., parent-offspring, siblings) have been reported, whereas the genetics of these cases have not yet been adequately studied.  We report the first familial case of EMPD involving three affected siblings.  The tumour-only multigene panel testing using surgical specimens revealed a heterozygous c.2997A>C (p.Glu999Asp) nonsynonymous variant in the proto-oncogene MET (NM_000245.4) in the three affected siblings. The germline multi-gene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members, including the two asymptomatic offspring (51 and 37 years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of familial cases of EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development.

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TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases

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TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases

Extramammary Paget disease (EMPD) predominantly manifests de novo as primary EMPD, with less than 30 % of cases associated with underlying internal malignancy (secondary EMPD). Differentiating primary from secondary EMPDs based solely on histopathology poses challenges, often necessitating supplementary screening, such as endoscopy or imaging studies, to definitively exclude underlying carcinomas like colonic adenocarcinoma. Recently, TRPS1 immunohistochemistry, initially identified as a sensitive and specific marker for carcinomas and mesenchymal tumors of mammary origin, has been proposed for EMPD. In this study, we conducted a systematic assessment of TRPS1 expression across 93 EMPD cases, comprising 82 primary EMPDs and 11 secondary EMPDs. Upon excluding cases of perianal primary EMPDs, the sensitivity and specificity of TRPS1 for primary EMPDs reached 100 %. Our findings suggest that TRPS1 expression holds notable sensitivity and specificity for primary EMPDs, particularly when arising from non-perianal cutaneous sites. Hence, in suitable clinical contexts, TRPS1 immunohistochemistry may emerge as a promising and valuable tool for distinguishing primary and secondary EMPDs.

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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: establishment of organoids and their biological analysis as a novel therapeutic target

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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: establishment of organoids and their biological analysis as a novel therapeutic target

Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear. Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy.

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TRPS1 expression is sensitive and specific for primary extramammary Paget disease

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TRPS1 expression is sensitive and specific for primary extramammary Paget disease

The most frequently utilized biomarkers for confirming the diagnosis of EMPD include CK7 and GATA3; however, these biomarkers lack specificity. The purpose of this study was to evaluate TRPS1, a newly described breast biomarker, in pagetoid neoplasms of the vulva, scrotum and anorectum. These results demonstrate that TRPS1 is a sensitive and specific biomarker for EMPD, and may be especially useful for excluding secondary involvement of the vulva by urothelial and anorectal carcinomas.

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Extramammary Paget’s disease: what do we know and how do we treat?

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Extramammary Paget’s disease: what do we know and how do we treat?

Signi!cant developments in understanding the pathogenesis of EMPD have been made, especially of the genomic aberrations associated with EMPD. This has allowed for the development and use of therapeutic options which may improve outcomes for patients with EMPD.

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