POU2F3 in SCLC: Clinicopathologic and genomic analysis with a focus on its diagnostic utility in neuroendocrine-low SCLC Journal Article
| Authors: | Baine, M. K.; Febres-Aldana, C. A.; Chang, J. C.; Jungbluth, A. A.; Sethi, S.; Antonescu, C. R.; Travis, W. D.; Hsieh, M. S.; Roh, M. S.; Homer, R. J.; Ladanyi, M.; Egger, J. V.; Lai, W. V.; Rudin, C. M.; Rekhtman, N. |
| Article Title: | POU2F3 in SCLC: Clinicopathologic and genomic analysis with a focus on its diagnostic utility in neuroendocrine-low SCLC |
| Abstract: | Introduction: POU2F3 is a recent marker of a small cell lung carcinoma (SCLC) subtype related to chemosensory tuft cells (SCLC-P). The characteristics of SCLC-P have not been fully defined, and the data on POU2F3 expression in other lung tumors are scarce. Methods: We screened 254 SCLC for POU2F3 expression and comprehensively analyzed histopathologic, genomic, and clinical characteristics of POU2F3-positive tumors. We also explored POU2F3 expression in other major lung cancer types (n = 433) and a targeted set of potential diagnostic mimics of SCLC (n = 123). Results: POU2F3 was expressed in 30 of 254 (12%) SCLC and was strongly associated with low expression of standard neuroendocrine markers (synaptophysin, chromogranin A, CD56, INSM1). Notably, POU2F3 was expressed in 75% of SCLC with entirely negative or minimal neuroendocrine marker expression (15/20) and was helpful in supporting the diagnosis of SCLC in such cases. Broad targeted next-generation sequencing revealed that SCLC-P (n = 12) exhibited enrichment in several alterations, including PTEN inactivation, MYC amplifications, and 20q13 amplifications, but similar rates of RB1 and TP53 alterations as other SCLC (n = 155). Beyond SCLC, POU2F3 expression was exclusively limited to large cell neuroendocrine carcinoma (12%) and basaloid squamous cell carcinoma (22%). Conclusions: This is the largest cohort of SCLC-P clinical samples to date, where we describe the diagnostic utility of POU2F3 in a challenging subset of SCLC with low or absent expression of standard neuroendocrine markers. The distinct genomic alterations in SCLC-P may offer a novel avenue for therapeutic targeting. The role of POU2F3 in a narrow subset of other lung cancer types warrants further study. © 2022 International Association for the Study of Lung Cancer |
| Keywords: | lung neoplasms; tumor marker; lung tumor; carcinoma; genomics; large cell carcinoma; repressor protein; repressor proteins; carcinoma, neuroendocrine; small cell lung cancer; small cell lung carcinoma; carcinoma, large cell; humans; human; biomarkers, tumor; pou2f3; insm1 protein, human; neuroendocrine-low; sclc-p; octamer transcription factor; pou2f3 protein, human; octamer transcription factors |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 17 |
| Issue: | 9 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-09-01 |
| Start Page: | 1109 |
| End Page: | 1121 |
| Language: | English |
| DOI: | 10.1016/j.jtho.2022.06.004 |
| PUBMED: | 35760287 |
| PROVIDER: | scopus |
| PMCID: | PMC9427708 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
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