Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases.
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
24 May 2024
24 May 2024
Historique:
revised:
16
04
2024
received:
23
10
2023
accepted:
09
05
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
24
5
2024
Statut:
aheadofprint
Résumé
Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions. Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases. Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Société Française de Dermatologie et de Pathologie Sexuellement Transmissible
Informations de copyright
© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.
Références
Goldman P, Pinkus H, Rogin JR. Eccrine poroma: tumors exhibiting features of the epidermal sweat duct unit. AMA Arch. Derm. 1956; 74; 511–521.
Harvell JD, Kerschmann RL, LeBoit PE. Eccrine or apocrine poroma? Six poromas with divergent adnexal differentiation. Am. J. Dermatopathol. 1996; 18; 1–9.
Sawaya JL, Khachemoune A. Poroma: a review of eccrine, apocrine, and malignant forms. Int. J. Dermatol. 2014; 53; 1053–1061.
Horenstein MG, Sandoval MP, Lo Y, Jacob J. Holocrine Poroma: a distinctive adnexal tumor. Am. J. Dermatopathol. 2018; 40; 401–408.
Kazakov DV, Kutzner H, Spagnolo DV et al. Sebaceous differentiation in poroid neoplasms: report of 11 cases, including a case of metaplastic carcinoma associated with apocrine poroma (sarcomatoid apocrine porocarcinoma). Am. J. Dermatopathol. 2008; 30; 21–26.
Robson A, Greene J, Ansari N et al. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Am. J. Surg. Pathol. 2001; 25; 710–720.
Kervarrec T, Pissaloux D, Tirode F et al. Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: an update. Histopathology 2023; 84; 266–278.
Le LP, Dias‐Santagata D, Pawlak AC et al. Apocrine‐eccrine carcinomas: molecular and immunohistochemical analyses. PLoS One 2012; 7; e47290.
Macagno N, Sohier P, Kervarrec T et al. Recent advances on immunohistochemistry and molecular biology for the diagnosis of adnexal sweat gland tumors. Cancers (Basel) 2022; 14; 476.
Hile G, Harms PW. Update on molecular genetic alterations of cutaneous adnexal neoplasms. Surg Pathol Clin 2021; 14; 251–272.
Westphal D, Garzarolli M, Sergon M et al. High tumour mutational burden and EGFR/MAPK pathway activation are therapeutic targets in metastatic porocarcinoma. Br. J. Dermatol. 2021; 185; 1186–1199.
Sekine S, Kiyono T, Ryo E et al. Recurrent YAP1‐MAML2 and YAP1‐NUTM1 fusions in poroma and porocarcinoma. J. Clin. Invest. 2019; 129; 3827–3832.
Kervarrec T, Frouin E, Collin C et al. Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1‐deficient skin carcinoma. Histopathology 2023; 82; 885–898.
Szulzewsky F, Holland EC, Vasioukhin V. YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance. Dev. Biol. 2021; 475; 205–221.
Kervarrec T, Pissaloux D, Paindavoine S et al. Recurrent PAK2 rearrangements in poroma with folliculo‐sebaceous differentiation. Histopathology 2023; 83; 310–319.
Thibodeau ML, Bonakdar M, Zhao E et al. Whole genome and whole transcriptome genomic profiling of a metastatic eccrine porocarcinoma. NPJ Precis Oncol. 2018; 2; 8.
Calonje E, Kazakov DV, Requena L, Harms PW. Porocarcinoma. In Skin tumours. 5th ed. Lyon: International Agency for Research on Cancer, 2023.
Cellier L, Perron E, Pissaloux D et al. Cutaneous Melanocytoma with CRTC1‐TRIM11 fusion: report of 5 cases resembling clear cell sarcoma. Am. J. Surg. Pathol. 2018; 42; 382–391.
Macagno N, Pissaloux D, de la Fouchardière A et al. Wholistic approach—transcriptomic analysis and beyond using archival material for molecular diagnosis. Genes Chromosomes Cancer. 2021; 61(6): 382‐393accepted, in press.
Dobin A, Davis CA, Schlesinger F et al. STAR: ultrafast universal RNA‐seq aligner. Bioinformatics 2013; 29; 15–21.
Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013; 14; R36.
Haas BJ, Dobin A, Stransky N et al. STAR‐fusion: fast and accurate fusion transcript detection from RNA‐Seq. Bioinformatics: Biorxiv, 2017. https://doi.org/10.1101/120295.
Ge H, Liu K, Juan T, Fang F, Newman M, Hoeck W. FusionMap: detecting fusion genes from next‐generation sequencing data at base‐pair resolution. Bioinformatics 2011; 27; 1922–1928.
Benelli M, Pescucci C, Marseglia G, Severgnini M, Torricelli F, Magi A. Discovering chimeric transcripts in paired‐end RNA‐seq data by using EricScript. Bioinformatics 2012; 28; 3232–3239.
Nicorici D, Satalan M, Edgren H et al. FusionCatcher—a tool for finding somatic fusion genes in paired‐end RNA‐sequencing data. Bioinformatics 2014. https://doi.org/10.1101/011650.
Uhrig S, Ellermann J, Walther T et al. Accurate and efficient detection of gene fusions from RNA sequencing data. Genome Res. 2021; 31; 448–460.
McKenna A, Hanna M, Banks E et al. The genome analysis toolkit: a MapReduce framework for analyzing next‐generation DNA sequencing data. Genome Res. 2010; 20; 1297–1303.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high‐throughput sequencing data. Nucleic Acids Res. 2010; 38; e164.
Macagno N, Kervarrec T, Thanguturi S et al. SOX10‐internal tandem duplications and PLAG1 or HMGA2 fusions segregate eccrine‐type and apocrine‐type cutaneous mixed tumors. Mod. Pathol. 2024; 37; 100430.
Zahn J, Chan MP, Wang G et al. Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma. J. Cutan. Pathol. 2019; 46; 659–664.
Boyd N, Dancey JE, Gilks CB, Huntsman DG. Rare cancers: a sea of opportunity. Lancet Oncol. 2016; 17; e52–e61.
Yu F‐X, Zhao B, Guan K‐L. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 2015; 163; 811–828.
Sabra H, Brunner M, Mandati V et al. β1 integrin‐dependent Rac/group I PAK signaling mediates YAP activation of yes‐associated protein 1 (YAP1) via NF2/merlin. J. Biol. Chem. 2017; 292; 19179–19197.
Xing J, Wang Z, Xu H et al. Pak2 inhibition promotes resveratrol‐mediated glioblastoma A172 cell apoptosis via modulating the AMPK‐YAP signaling pathway. J. Cell. Physiol. 2020; 235; 6563–6573.
Yao D, Li C, Rajoka MSR et al. P21‐activated kinase 1: emerging biological functions and potential therapeutic targets in cancer. Theranostics 2020; 10; 9741–9766.
Rane CK, Minden A. P21 activated kinase signaling in cancer. Semin. Cancer Biol. 2019; 54; 40–49.
Tan X, Tong L, Li L et al. Loss of Smad4 promotes aggressive lung cancer metastasis by de‐repression of PAK3 via miRNA regulation. Nat. Commun. 2021; 12; 4853.
Huynh N, Wang K, Yim M et al. Depletion of p21‐activated kinase 1 up‐regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis. BMC Cancer 2017; 17; 431.
Tormo‐Mainar S, Vidal J, Salido M, Pujol RM, Deza G. YAP1‐NUTM1 gene fusion in eccrine Porocarcinoma with late metastatic recurrence: a case report. Acta Derm. Venereol. 2022; 102; adv00752.
Christensen DJ, Tuluc M. Porocarcinoma with YAP1‐NUTM1 fusion presenting as a NUT immunohistochemistry‐positive lymph node metastasis. J. Cutan. Pathol. 2023; 50; 410–414.
Harms PW, Hovelson DH, Cani AK et al. Porocarcinomas harbor recurrent HRAS‐activating mutations and tumor suppressor inactivating mutations. Hum. Pathol. 2016; 51; 25–31.