Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC?
Small cell lung cancer (SCLC) subtype classification, based on high-level expression of key transcriptional regulators; ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y), has recently been proposed. YAP1 (and POU2F3) has attracted attention as an important factor for non-neuroendo...
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| Format: | Article |
| Language: | English |
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IMR Press
2022-03-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703108 |
| _version_ | 1818355109428461568 |
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| author | Hitomi Kawai Ryouta Matsuoka Takeshi Ito Daisuke Matsubara |
| author_facet | Hitomi Kawai Ryouta Matsuoka Takeshi Ito Daisuke Matsubara |
| author_sort | Hitomi Kawai |
| collection | DOAJ |
| description | Small cell lung cancer (SCLC) subtype classification, based on high-level expression of key transcriptional regulators; ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y), has recently been proposed. YAP1 (and POU2F3) has attracted attention as an important factor for non-neuroendocrine (non-NE) phenotypic subtyping of SCLC. However, subsequent studies reported that YAP1 expression alone cannot define a single group in primary SCLC, which makes it difficult to understand what SCLC-Y is by focusing only on SCLC. In this review, we concluded that YAP1 is an essential anti-neuroendocrine factor in both SCLC and non-small cell lung cancer (NSCLC) based on previous studies, including our own analysis of the cell lines and primary tumors of SCLC and NSCLC. The classification of SCLC-Y is a concept mainly established from the analysis of cell lines, and SCLC-Y cell lines correspond to “variant type” SCLC cell lines. Primary SCLC and large cell neuroendocrine carcinoma (LCNEC) are typically heterogeneous tumors composed mostly of NE-type cells, but they contain a small number of non-NE-type cells. Importantly, individual cells with NE features exhibit YAP1 loss, whereas the non-NE-type cells exhibit YAP1 expression. Although rare in primary SCLC, some cases of primary LCNEC have many YAP1-positive cells, which is correlated with chemotherapy resistance. YAP1 staining may be useful in the exclusion diagnosis of SCLC or in the selection of treatment for LCNEC. |
| first_indexed | 2024-12-13T19:36:05Z |
| format | Article |
| id | doaj.art-46e39965d7974fe59cc97aed002f3bdf |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-12-13T19:36:05Z |
| publishDate | 2022-03-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-46e39965d7974fe59cc97aed002f3bdf2022-12-21T23:33:48ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-03-0127310810.31083/j.fbl2703108S2768-6701(22)00446-4Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC?Hitomi Kawai0Ryouta Matsuoka1Takeshi Ito2Daisuke Matsubara3Department of Pathology, Tsukuba University Hospital, 305-8576 Ibaraki, JapanDepartment of Pathology, Tsukuba University Hospital, 305-8576 Ibaraki, JapanDivision of Molecular Pathology, Institute of Medical Science, University of Tokyo, 108-0071 Tokyo, JapanDepartment of Pathology, Tsukuba University Hospital, 305-8576 Ibaraki, JapanSmall cell lung cancer (SCLC) subtype classification, based on high-level expression of key transcriptional regulators; ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y), has recently been proposed. YAP1 (and POU2F3) has attracted attention as an important factor for non-neuroendocrine (non-NE) phenotypic subtyping of SCLC. However, subsequent studies reported that YAP1 expression alone cannot define a single group in primary SCLC, which makes it difficult to understand what SCLC-Y is by focusing only on SCLC. In this review, we concluded that YAP1 is an essential anti-neuroendocrine factor in both SCLC and non-small cell lung cancer (NSCLC) based on previous studies, including our own analysis of the cell lines and primary tumors of SCLC and NSCLC. The classification of SCLC-Y is a concept mainly established from the analysis of cell lines, and SCLC-Y cell lines correspond to “variant type” SCLC cell lines. Primary SCLC and large cell neuroendocrine carcinoma (LCNEC) are typically heterogeneous tumors composed mostly of NE-type cells, but they contain a small number of non-NE-type cells. Importantly, individual cells with NE features exhibit YAP1 loss, whereas the non-NE-type cells exhibit YAP1 expression. Although rare in primary SCLC, some cases of primary LCNEC have many YAP1-positive cells, which is correlated with chemotherapy resistance. YAP1 staining may be useful in the exclusion diagnosis of SCLC or in the selection of treatment for LCNEC.https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703108reviewyap1sclclcnechgnecsclc-ysclc-ichemo-sensitivity |
| spellingShingle | Hitomi Kawai Ryouta Matsuoka Takeshi Ito Daisuke Matsubara Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? Frontiers in Bioscience-Landmark review yap1 sclc lcnec hgnec sclc-y sclc-i chemo-sensitivity |
| title | Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? |
| title_full | Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? |
| title_fullStr | Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? |
| title_full_unstemmed | Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? |
| title_short | Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC? |
| title_sort | molecular subtypes of high grade neuroendocrine carcinoma hgnec what is yap1 positive hgnec |
| topic | review yap1 sclc lcnec hgnec sclc-y sclc-i chemo-sensitivity |
| url | https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703108 |
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