Journal of the European Academy of Dermatology and VenereologyVolume 36, Issue 9 p. e724-e726 Letter to the Editor Upregulated androgen receptor variant-7 mRNA and protein in extramammary Paget's disease S. Yamada-Kanazawa, S. Yamada-Kanazawa orcid.org/0000-0001-9276-3563 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorM.T. Mijiddorj, M.T. Mijiddorj Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorI. Kajihara, Corresponding Author I. Kajihara [email protected] Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan These authors contributed equally to this study.Correspondence: I. Kajihara. E-mail: [email protected]Search for more papers by this authorH. Kanemaru, H. Kanemaru Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Sawamura, S. Sawamura orcid.org/0000-0003-1697-9316 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorK. Makino, K. Makino Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorJ. Aoi, J. Aoi orcid.org/0000-0002-0988-2471 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this author S. Yamada-Kanazawa, S. Yamada-Kanazawa orcid.org/0000-0001-9276-3563 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorM.T. Mijiddorj, M.T. Mijiddorj Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorI. Kajihara, Corresponding Author I. Kajihara [email protected] Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan These authors contributed equally to this study.Correspondence: I. Kajihara. E-mail: [email protected]Search for more papers by this authorH. Kanemaru, H. Kanemaru Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Sawamura, S. Sawamura orcid.org/0000-0003-1697-9316 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorK. Makino, K. Makino Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorJ. Aoi, J. Aoi orcid.org/0000-0002-0988-2471 Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanSearch for more papers by this author First published: 19 May 2022 https://doi.org/10.1111/jdv.18229 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume36, Issue9September 2022Pages e724-e726 RelatedInformation

Abstract Background Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD‐1 (an immune checkpoint inhibitor), is more effective against MMR‐deficient tumours than against MMR‐proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). Objectives To evaluate the status of MMR in patients with EMPD. Materials & Methods One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab). Results MSI testing showed the occurrence rates of MSI‐high (more than two markers are unstable), MSI‐low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. Conclusion The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

None declared. The data that support the findings of this study are available from the corresponding author upon reasonable request.

BACKGROUND:Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers.OBJECTIVES:To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD.METHODS:cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction.RESULTS:Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy.CONCLUSIONS:Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.

BACKGROUND:Dermatomyositis (DM) and systemic lupus erythematosus (SLE) have common skin features, including dermal mucin deposition and interferon signature, although their roles are unknown.OBJECTIVES:To identify common or specific molecular changes in DM and SLE skin.METHODS:Proteomic analysis was performed using DM and healthy skin. Glycosaminoglycans were analysed by high-performance liquid chromatography.RESULTS:The expression of 60 proteins was upregulated or downregulated in DM skin compared with healthy skin in the proteomic analysis. Among those proteins, PSMB9, an immunoproteasome subunit, was upregulated in the epidermis of DM and SLE, but not in other skin diseases. Furthermore, versican V1, a core protein for glycosaminoglycans, was upregulated, while type I collagen was downregulated in the dermis of DM and SLE skin. Interferon stimulated PSMB9 expression in cultured keratinocytes and reduced collagen expression in dermal fibroblasts, but did not affect versican expression. The PSMB9 knock-down in keratinocytes led to significant suppression of transforming growth factor (TGF)-β2 and TGF-β3, inducers of versican synthesis. TGF-β3 expression was upregulated in both DM and SLE, while TGF-β2 expression was increased only in the DM epidermis. ΔDiHS-diS1, a component of heparan sulfate, was significantly increased only in DM. TGF-β2 expression significantly increased the ΔDiHS-diS1 expression in dermal fibroblasts in vitro.CONCLUSIONS:The interferon signature in DM and SLE skin reduces collagen in dermal fibroblasts, whereas overexpression of PSMB9 induced by interferon stimulates versican inducers in epidermal keratinocytes. In addition, the TGF-β2-ΔDiHS-diS1 pathway may be responsible for the specific molecular change in DM skin.

Background. The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis.Aim. To examine the role of JNK isoforms in metastasis, proliferation, migration and invasion of the malignant melanoma (MM) cell lines SK-MEL-28, SK-MEL-3 and WM164, using a kinase-specific inhibitor or isoform-specific small interfering (si) RNAs.Results. SK-MEL-3, a cell line established from metastatic MM, showed slightly increased phosphorylation of both JNK1 and JNK2, whereas WM164, a cell line derived from primary MM, showed significant phosphorylation of JNK1. A JNK inhibitor, SP600125, inhibited cell proliferation of SK-MEL-3 but not SK-MEL-28 or WM164. Transfection of JNK1-specific siRNA reduced the migratory activity of WM164 cells, while silencing of either JNK1 or JNK2 strongly suppressed the invasive activity of SK-MEL-3.Conclusions. Our study suggests that JNK isoforms have different roles in MM. Metastasis of MM may be regulated by JNK2, while invasion is regulated by both JNK1 and JNK2. JNK1 and JNK2 respectively mediate cell migration and cell proliferation. Further understanding of the specific roles of JNK isoforms in the pathogenesis of MM may lead to the development of therapies targeting specific isoforms.

BACKGROUND:Epidermal growth factor receptor (EGFR) is known to be abnormally expressed in many human carcinomas, suggesting that there may be an increase in serum EGFR levels in patients with malignant melanoma (MM) and that this might be a possible new tumour marker.AIM:To assess whether serum EGFR levels might be a marker of MM.METHODS:Serum samples were obtained from 66 patients with MM and 12 healthy controls, and EGFR levels were measured by double-determinant ELISA.RESULTS:Patients with in situ or stage I MM had significantly higher serum EGFR levels compared with healthy controls. Interestingly, serum EGFR levels decreased gradually with the stage of the tumour, being highest at stage I and lowest at stage IV. There was also a trend towards a reverse correlation between tumour thickness and serum EGFR levels. Moreover, a longitudinal study identified a trend for serum EGFR levels in patients with preoperative MM to decrease compared with patients with recurrent MM.CONCLUSIONS:To our knowledge, this is the first report investigating the serum EGFR levels of patients with MM, and gives new insight into the relationship between EGFR and MM. We found that serum EGFR levels were significantly increased in patients with early-stage MM such as in situ and stage I tumours. Measurements of serum EGFR levels might be of clinical value in the detection of early-stage MM.

Clinical and Experimental DermatologyVolume 37, Issue 2 p. 183-184 Viewpoints in dermatology •Correspondence Cutaneous type adult T-cell leukaemia/lymphoma successfully treated with narrowband ultraviolet B phototherapy H. Kudo, H. Kudo Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorK. Sakai, K. Sakai Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorM. Jinnin, M. Jinnin Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorH. Ihn, H. Ihn Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this author H. Kudo, H. Kudo Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorK. Sakai, K. Sakai Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorM. Jinnin, M. Jinnin Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this authorH. Ihn, H. Ihn Department of Dermatology and Plastic Surgery, Faculty of Life Science, Kumamoto University, Kumamoto, Japan E-mail: satoshi.fukushima.tb@gmail.comSearch for more papers by this author First published: 15 November 2011 https://doi.org/10.1111/j.1365-2230.2011.04141.xCitations: 6 Conflict of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume37, Issue2March 2012Pages 183-184 RelatedInformation

Journal of the European Academy of Dermatology and VenereologyVolume 26, Issue 1 p. 123-125 LETTER TO THE EDITOR Clinical significance of cobblestone appearance on the skin of patients with systemic sclerosis I. Kajihara, I. Kajihara Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorM. Jinnin, Corresponding Author M. Jinnin M. Jinnin. E-mail:mjin@kumamoto-u.ac.jpSearch for more papers by this authorT. Makino, T. Makino Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorA. Toihata Yonemitsu, A. Toihata Yonemitsu Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorK. Sakai, K. Sakai Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorH. Ihn, H. Ihn Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this author I. Kajihara, I. Kajihara Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorM. Jinnin, Corresponding Author M. Jinnin M. Jinnin. E-mail:mjin@kumamoto-u.ac.jpSearch for more papers by this authorT. Makino, T. Makino Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorA. Toihata Yonemitsu, A. Toihata Yonemitsu Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorK. Sakai, K. Sakai Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorS. Masuguchi, S. Masuguchi Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorS. Fukushima, S. Fukushima Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this authorH. Ihn, H. Ihn Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, JapanSearch for more papers by this author First published: 09 March 2011 https://doi.org/10.1111/j.1468-3083.2011.04007.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume26, Issue1January 2012Pages 123-125 RelatedInformation

Background. Recently, increased evidence has shown that serum micro (mi)RNA levels are a useful biomarker for the diagnosis, prognosis and therapeutic value of various diseases. However, serum miRNA has not been investigated in patients with systemic sclerosis (SSc), to our knowledge. Aim. To investigate the possibility that serum levels of Homo sapiens miR-142 stemloop (hsa-miR-142-3p), one of the miRNAs regulating the expression of integrin aV, could be a specific disease marker for SSc. Methods. Serum samples were obtained from 61 patients with SSc and 20 healthy controls. Patients with systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma spectrum disorder (SSD), who did not fulfil American College of Rheumatology criteria for SSc but might develop SSc in the future, were included as disease controls in this study. miRNAs were purified from serum, and miR-142-3p levels were measured with a quantitative real-time PCR assay. Results. Serum miR-142-3p levels in patients with SSc were significantly higher than in patients with SSD, SLE or DM, and healthy control groups. Patients with increased miR-142-3p levels tended to have a short sublingual frenulum. Conclusions. Our data indicate that serum levels of miR-142-3p may be elevated specifically in patients with SSc, correlating with the severity of this disease, and may be useful diagnostic markers for the presence of SSc and for the differentiation of SSc from SSD.

Background. Recently, increased evidence has shown that serum micro (mi)RNA levels are a useful biomarker for the diagnosis, prognosis and therapeutic value of various diseases. However, serum miRNA has not been investigated in patients with systemic sclerosis (SSc), to our knowledge.Aim. To investigate the possibility that serum levels of Homo sapiens miR-142 stemloop (hsa-miR-142-3p), one of the miRNAs regulating the expression of integrin aV, could be a specific disease marker for SSc.Methods. Serum samples were obtained from 61 patients with SSc and 20 healthy controls. Patients with systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma spectrum disorder (SSD), who did not fulfil American College of Rheumatology criteria for SSc but might develop SSc in the future, were included as disease controls in this study. miRNAs were purified from serum, and miR-142-3p levels were measured with a quantitative real-time PCR assay.Results. Serum miR-142-3p levels in patients with SSc were significantly higher than in patients with SSD, SLE or DM, and healthy control groups. Patients with increased miR-142-3p levels tended to have a short sublingual frenulum.Conclusions. Our data indicate that serum levels of miR-142-3p may be elevated specifically in patients with SSc, correlating with the severity of this disease, and may be useful diagnostic markers for the presence of SSc and for the differentiation of SSc from SSD.

BACKGROUND:Psoriasis is a chronic inflammatory skin disease characterized by intense proliferation and abnormal differentiation of keratinocytes, although the pathogenesis is still not completely clarified.OBJECTIVES:We investigated the mechanism of keratinocyte proliferation seen in psoriasis, focusing on microRNA (miRNA).MATERIALS AND METHODS:miRNAs were extracted from tissues and sera of psoriasis, atopic dermatitis and healthy control. To determine pathogenic miRNAs, we performed miRNA polymerase chain reaction (PCR) array analysis. The results were confirmed with quantitative real-time PCR, in situ hybridization, immunohistochemistry, transient transfection of siRNA and inhibitor in cultured keratinocytes and Western blotting.RESULTS:PCR array analysis using tissue miRNA demonstrated miR-424 level was markedly decreased in psoriasis skin in vivo. Protein expression of mitogen-activated protein kinase kinase 1 (MEK1) or cyclin E1, predicted target genes of miR-424, was increased in psoriatic skin, although their mRNA levels were not. The transfection of specific inhibitor of miR-424 in normal human keratinocytes led to upregulation of MEK1 or cyclin E1 protein, and resulted in increased cell proliferation. On the other hand, cell number was significantly decreased when cells were transfected with siRNA for MEK1 or cyclin E1. Furthermore, we first investigated serum miRNA levels in psoriasis. Although not significant, serum miR-424 concentration tended to be decreased in patients with psoriasis compared with healthy controls.CONCLUSIONS:Decreased miR-424 expression and subsequently increased MEK1 or cyclin E1 may play a key role in the pathogenesis of psoriasis. Investigation of the regulatory mechanisms of keratinocyte proliferation by miRNA may lead to new treatments and a disease activity marker.

Matsushita, Shigeto M.D.; Ishihara, Tsuyoshi M.D.; Masuguchi, Shinichi M.D.; Gyoutoku, Takashi M.D.; Ono, Tomomichi M.D. Author Information