| Autor: |
Kianoosh Keyhanian, William J. Phillips, Benjamin S. Yeung, Marcio Gomes, Bryan Lo, Harmanjatinder S. Sekhon |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Diagnostic Pathology, Vol 17, Iss 1, Pp 1-11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1746-1596 |
| DOI: |
10.1186/s13000-022-01223-6 |
| Popis: |
Abstract Background Neuroendocrine (NE) differentiation is widely studied in non-small cell lung carcinomas (NSCLC) however, its significance remains unclear in basaloid squamous cell carcinomas (B-SqCC). This study aims to assess the extent of NE differentiation in B-SqCC and characterize the underlying molecular process. Methods This study evaluated resected B-SqCC, small cell lung cancer (SCLC) and poorly differentiated SqCC (PD-SqCC) from 2005 to 2020 at the Ottawa Hospital. Samples were subject to pathological review, immunohistochemistry (IHC) and survival analysis. Gene expression analysis was performed on B-SqCC samples exhibiting NE+ and NE- regions (paired samples) to identify differentially expressed genes (DEGs). These DEGs were subsequently validated in unpaired B-SqCC and TCGA samples. Results B-SqCC cases were more likely to exhibit nuclear molding, resetting and peripheral palisading than PD-SqCC. B-SqCC were also more likely to demonstrate NE differentiation compared to PD-SqCC (p = 0.006). Pure basaloid squamous cell carcinoma (PB-SqCC) experienced poorer disease-free survival (HR = 3.12, p = 0.043) adjusted for stage. Molecular characterization of paired B-SqCC samples demonstrated DEGs implicated in NOTCH signaling, SCLC and pulmonary neuroendocrine differentiation. Hierarchical clustering using discovered DEGs in unpaired B-SqCC samples distinguished tumors based on NE status (p = 0.048). Likewise, clustering The Cancer Genome Atlas (TCGA) samples with DEGs distinguished B-SqCC from SqCC samples (p = 0.0094). Conclusion This study provides IHC and molecular evidence of significant NE-differentiation in B-SqCC and demonstrates their aggressive clinical behavior. These findings suggest that B-SqCC are biologically distinct from SqCC and share characteristics with SCLC. |
| Databáze: |
Directory of Open Access Journals |
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