Authors
Renqing Wang, Chen Qian, Jun Du, Wei Wang, Yin He, Tingting Chen, Jie Yin, Yuanzi Ye, Yao Fu, Xiangshan Fan
Published in
Human pathology. Pages 106219. Aug 12, 2026. Epub Aug 12, 2026.
Abstract
Non-small cell lung carcinomas showing co-expression of TTF-1 and p40 in sampled tumor tissue are rare, diagnostically challenging, and not formally recognized in the current WHO classification of thoracic tumors. We analyzed 15 pulmonary carcinomas with TTF-1/p40 co-expression to characterize their clinicopathologic features and molecular alterations. The cohort consisted predominantly of male patients and was composed mainly of high-grade, poorly differentiated tumors. All cases demonstrated diffuse nuclear co-expression of TTF-1 and p40 by immunohistochemistry. Whole-exome sequencing, performed in 12 cases, revealed frequent TP53 alterations (9/12), occasional concurrent RB1 alterations, and a rare FGFR3::TACC3 fusion, which was further validated by FISH. Two tumors with prominent lymphoid stroma were positive for Epstein-Barr virus-encoded RNA and lacked TP53 alterations, suggesting additional biological diversity within this phenotype. Follow-up data were available for 13 patients (range, 1-29 months); 4 died of disease and 9 were alive at last follow-up. Two additional patients were lost to follow-up. Collectively, these findings suggest that pulmonary carcinomas showing TTF-1/p40 co-expression in sampled tissue comprise a heterogeneous clinicopathologic and molecular group rather than a currently definable distinct entity. Despite the small sample size and the inclusion of several biopsy-only cases, this study provides a descriptive basis for future investigation of this unusual immunophenotypic pattern.
PMID:
42586248
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.
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