Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: Clinicopathological and genomic features of 14 rare biphenotypic tumours Journal Article
| Authors: | Savari, O.; Febres-Aldana, C.; Chang, J. C.; Fanaroff, R. E.; Ventura, K.; Bodd, F.; Paik, P.; Vundavalli, M.; Saqi, A.; Askin, F. B.; Travis, W. D.; Rekhtman, N. |
| Article Title: | Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: Clinicopathological and genomic features of 14 rare biphenotypic tumours |
| Abstract: | Thyroid transcription factor 1 (TTF1) and p40 are widely-utilized diagnostic markers of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), respectively. Diffuse coexpression of TTF1 and p40 has been described in only rare case reports. In a multi-institutional study, we collected the largest cohort of these unusual tumours to-date (n = 14), with the goal of elucidating their clinicopathological and genomic characteristics. Lung tumours with diffuse coexpression (labelling 50–100% tumour cells) of TTF1 clone 8G7G3/1 and p40 clone BC28 were identified. Detailed clinicopathological and immunohistochemical parameters were analyzed. Eight tumours were analyzed by next-generation sequencing (NGS) and the results were compared to those in > 9 K LUAD and > 1 K LUSC. All tumours with diffuse TTF1/p40 coexpression were poorly differentiated non-small cell lung carcinomas (NSCLC), 42% of which had basaloid features. Some tumours exhibited focal keratinization (14%), napsin A and/or mucicarmine labelling (46%) or both squamous and glandular features (7%). NGS revealed a uniquely high rate of FGFR1 amplifications (70%) compared to either LUAD (0.7%, P < 0.0001) or LUSC (11%, P = 0.001). LUAD-type targetable driver alterations were identified in 38% of cases (one EGFR, two KRAS G12C). The tumours were clinically aggressive, exhibiting metastatic disease in most patients. Lung carcinomas with diffuse TTF1/p40 coexpression represent poorly differentiated NSCLCs with frequent basaloid features, but some show evidence of focal squamous, glandular or dual differentiation with a distinctly high rate of FGFR1 amplifications. The presence of targetable LUAD-type alterations (EGFR, KRAS G12C) emphasizes the importance of molecular testing in these tumours. © 2022 John Wiley & Sons Ltd. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; protein expression; aged; primary tumor; unclassified drug; dna binding protein; human cell; genetics; dna-binding proteins; clinical feature; histopathology; squamous cell carcinoma; carcinoma, squamous cell; comparative study; tumor volume; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; epidermal growth factor receptor 2; cohort analysis; transcription factor; cell differentiation; transcription factors; lung tumor; genome analysis; lung adenocarcinoma; thyroid nuclear factor 1; multicenter study; lung; genomics; lung carcinoma; k ras protein; b raf kinase; fibroblast growth factor receptor 1; scatter factor receptor; synaptophysin; standardized uptake value; non small cell lung cancer; dna methyltransferase 3a; protein p40; nsclc; chromogranin a; ttf1; ttf1 protein, human; cd56 antigen; protein kinase lkb1; keratinization; p40; high throughput sequencing; pold1 protein; very elderly; humans; human; male; female; article; napsin a; fgfr1; squamous cell lung carcinoma; pole protein; pik3ca protein; homeobox protein nkx 2.1; insm1 protein; mucicarmine |
| Journal Title: | Histopathology |
| Volume: | 82 |
| Issue: | 2 |
| ISSN: | 0309-0167 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-01-01 |
| Start Page: | 242 |
| End Page: | 253 |
| Language: | English |
| DOI: | 10.1111/his.14801 |
| PUBMED: | 36130728 |
| PROVIDER: | scopus |
| PMCID: | PMC10501689 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding author is MSK author Natasha Rekhtman -- Export Date: 3 January 2023 -- Source: Scopus |
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