SATB2 is expressed in Merkel cell carcinoma

The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch-gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell-neurite complexes, Meissner-like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20 , chromogranin A and synaptophisin ) Merkel cells. Most of them were in close contact with Piezo2 nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2 , but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non-nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans.

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“…; Fukuhara et al. ). We demonstrated they are CK20, which is in line with the epithelial (Morrison et al.…”

Section: Discussionmentioning

confidence: 97%

“…; Fukuhara et al. ]. Non‐specific binding was reduced by incubating the sections for 30 min with a solution of 25% calf bovine serum in Tris buffer solution (TBS).…”

Section: Methodsmentioning

confidence: 99%

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity

et al. 2017

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“…reported SATB2 positivity in 40% of ‘carcinoids’, not further specified . This same group reported no staining in 10 ‘carcinoids’ in a subsequent study focused on SATB2 expression in NECs . Lin et al .…”

Section: Discussionmentioning

confidence: 98%

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

Bellizzi

2019

Histopathology

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Aims Special AT‐rich sequence‐binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well‐differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms. Methods and results Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0–3+), with an H‐score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well‐differentiated neoplasms (P < 0.0001). Expression in lower GI tract NETs (median H‐score of 255) was stronger than in other positive tumours (median H‐score of 7) (P < 0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H‐score of 300), 33% of lung NECs (median H‐score of 23), and 60% of extrapulmonary visceral NECs (median H‐score of 110), with stronger expression in Merkel cell carcinoma (P < 0.001). At an H‐score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma. Conclusions SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.

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“…In addition to colorectal cancer, SATB2 expression has also been described recently in other tumours, including carcinomas of the gastrointestinal tract such as small intestinal carcinoma, appendical mucinous neoplasm, pancreatic adenocarcinoma and oesophageal squamous cell carcinoma, as well as neoplasms of neuroectodermal and mesenchymal origin; for example, Merkel cell carcinoma, neuroendocrine tumours and osteosarcoma . However, as > 85% of CRC were SATB2‐positive in two large studies comprising > 1800 and > 100 CRC cases in total, this marker has been advocated to determine colorectal origin .…”

Section: Discussionmentioning

confidence: 99%

Role of conventional immunomarkers, HNF4‐α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas

et al. 2018

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SATB2 is expressed in Merkel cell carcinoma

Cited by 42 publications

References 11 publications

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

Role of conventional immunomarkers, HNF4‐α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas

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