Nestin is expressed in HMB‐45 negative melanoma cells in dermal parts of nodular melanoma

Abstract

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

Superficial spreading and nodular melanoma are distinct biological entities

“…Kanoh and colleagues examined 15 NM and 12 SSM formalin-fixed, paraffin-embedded (FFPE) tissues for levels of nestin, a marker or neural stem cells that has recently been suggested to be a marker of melanoma cells of origin [88]. They found nestin immunoreactivity in all amelanotic and 80% of the melanotic NMs while expression was only seen in 17% of the SSM cases [28]. However, this small sample size was not matched for thickness and previous reports have shown that nestin expression was significantly correlated with the stage of melanomas [89].…”

“…It is currently accepted that the speed of dermal invasion is the only aspect that separates the NM and SSM subtypes [19, 20]. Nevertheless, evidence has emerged challenging this linear model of progression and suggesting that these two subtypes are distinct entities [16, 21–28]. …”

Immunohistochemical and genetic profiles of melanomas with spindle cell morphology

“…Результаты нашего иссле-дования продемонстрировали выраженную экспрессию нестина в HMB45-негативных опухолях, отнесенных к смешанному и чистому десмопластическому варианту, что совпадает с данными работы M. Kanoh и соавт. [7], считающими нестин одним из основных диагностических а -результаты HRMA (зеленая кривая -образец без мутации, красная -образец с мутацией V600E, исследуемый образец указан стрелкой); б -результаты секвенирования (с.1799Т>А).…”

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

“…Nestin was also co-expressed with SOX9 and SOX10, which may contribute to its transcriptional up-regulation, in primary and secondary melanoma specimens and associated with a poor survival of melanoma patients [98][99][100][101] . The analyses by flow cytometry and quantitative reverse transcription-PCR (qRT-PCR) of the expression level of nestin performed on 23 tissue specimens from patients with stage Ⅲ-Ⅳ melanoma has also indicated that this stem cell-like marker was expressed at a higher level in stage Ⅳ patients compared to stage Ⅲ /Ⅳ with no evidence of disease [93] .…”

“…The immunohistochemical analysis of nestin, which is a neuroepithelial intermediate filament expressed in proliferative neuroectodermal progenitor cells during embryonic development and adult bulge areas-resident stem cells in hair follicle, has also indicated that its expression was significantly enhanced in primary and metastatic melanoma tissue specimens as compared to benign and normal melanocytes [96][97][98][99][100][101] . Nestin was also co-expressed with SOX9 and SOX10, which may contribute to its transcriptional up-regulation, in primary and secondary melanoma specimens and associated with a poor survival of melanoma patients [98][99][100][101] .…”