Bibliographic Details
| Title: |
Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma |
| Authors: |
Kianoosh Keyhanian, William J. Phillips, Benjamin S. Yeung, Marcio Gomes, Bryan Lo, Harmanjatinder S. Sekhon |
| Source: |
Diagnostic Pathology, Vol 17, Iss 1, Pp 1-11 (2022) |
| Publisher Information: |
BMC, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Pathology |
| Subject Terms: |
Basaloid squamous cell carcinoma, Neuroendocrine differentiation, Gene expression, Immunohistochemistry, NOTCH, Pathology, RB1-214 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1746-1596 |
| Relation: |
https://doaj.org/toc/1746-1596 |
| DOI: |
10.1186/s13000-022-01223-6 |
| Access URL: |
https://doaj.org/article/20ca97d557be4832bf8cd30ef0d85a5f |
| Accession Number: |
edsdoj.20ca97d557be4832bf8cd30ef0d85a5f |
| Database: |
Directory of Open Access Journals |
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