The expression of YAP1 and other transcription factors contributes to lineage plasticity in combined small cell lung carcinoma.
Humans
YAP-Signaling Proteins
/ metabolism
Small Cell Lung Carcinoma
/ pathology
Lung Neoplasms
/ pathology
Transcription Factors
/ metabolism
Male
Adaptor Proteins, Signal Transducing
/ genetics
Female
Middle Aged
Aged
Immunohistochemistry
Cell Lineage
Biomarkers, Tumor
/ genetics
Mutation
Cell Plasticity
Tumor Suppressor Protein p53
/ metabolism
Basic Helix-Loop-Helix Transcription Factors
/ metabolism
YAP1
combined small cell lung carcinoma
molecular marker
mosaic
plasticity
small cell carcinoma
small cell lung carcinoma
transcription factors
Journal
The journal of pathology. Clinical research
ISSN: 2056-4538
Titre abrégé: J Pathol Clin Res
Pays: England
ID NLM: 101658534
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
revised:
21
08
2024
received:
15
01
2024
accepted:
21
08
2024
medline:
17
9
2024
pubmed:
17
9
2024
entrez:
16
9
2024
Statut:
ppublish
Résumé
Lineage plasticity in small cell lung carcinoma (SCLC) causes therapeutic difficulties. This study aimed to investigate the pathological findings of plasticity in SCLC, focusing on combined SCLC, and elucidate the involvement of YAP1 and other transcription factors. We analysed 100 surgically resected SCLCs through detailed morphological observations and immunohistochemistry for YAP1 and other transcription factors. Component-by-component next-generation sequencing (n = 15 pairs) and immunohistochemistry (n = 35 pairs) were performed on the combined SCLCs. Compared with pure SCLCs (n = 65), combined SCLCs (n = 35) showed a significantly larger size, higher expression of NEUROD1, and higher frequency of double-positive transcription factors (p = 0.0009, 0.04, and 0.019, respectively). Notably, 34% of the combined SCLCs showed morphological mosaic patterns with unclear boundaries between the SCLC and its partner. Combined SCLCs not only had unique histotypes as partners but also represented different lineage plasticity within the partner. NEUROD1-dominant combined SCLCs had a significantly higher proportion of adenocarcinomas as partners, whereas POU2F3-dominant combined SCLCs had a significantly higher proportion of squamous cell carcinomas as partners (p = 0.006 and p = 0.0006, respectively). YAP1 expression in SCLC components was found in 80% of combined SCLCs and 62% of pure SCLCs, often showing mosaic-like expression. Among the combined SCLCs with component-specific analysis, the identical TP53 mutation was found in 10 pairs, and the identical Rb1 abnormality was found in 2 pairs. On immunohistochemistry, the same abnormal p53 pattern was found in 34 pairs, and Rb1 loss was found in 24 pairs. In conclusion, combined SCLC shows a variety of pathological plasticity. Although combined SCLC is more plastic than pure SCLC, pure SCLC is also a phenotypically plastic tumour. The morphological mosaic pattern and YAP1 mosaic-like expression may represent ongoing lineage plasticity. This study also identified the relationship between transcription factors and partners in combined SCLC. Transcription factors may be involved in differentiating specific cell lineages beyond just 'neuroendocrine'.
Identifiants
pubmed: 39283755
doi: 10.1002/2056-4538.70001
doi:
Substances chimiques
YAP-Signaling Proteins
0
YAP1 protein, human
0
Transcription Factors
0
Adaptor Proteins, Signal Transducing
0
Biomarkers, Tumor
0
Tumor Suppressor Protein p53
0
Basic Helix-Loop-Helix Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70001Subventions
Organisme : JSPS (Japan Society for the Promotion of Science) KAKENHI
ID : JP19K18213
Organisme : JSPS (Japan Society for the Promotion of Science) KAKENHI
ID : JP 22K16172
Informations de copyright
© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
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