In the case we report, the pulmonary-type adenocarcinoma was closely associated with a bronchial structure and exhibited diffuse positive immunohistochemical staining with TTF1, PE10, and napsin A. Molecular studies revealed no evidence of epidermal growth factor receptor mutation, a molecular alteration which may be found in primary pulmonary adenocarcinoma.
TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40.
We therefore analyzed 102 large-cell carcinomas by immunohistochemistry for TTF-1 and ΔNp63/p40 as classifiers for adenocarcinoma and squamous cell carcinoma, respectively, and correlated the resulting subtypes with nine therapeutically relevant genetic alterations characteristic of adenocarcinoma (EGFR, KRAS, BRAF, MAP2K1/MEK1, NRAS, ERBB2/HER2 mutations and ALK rearrangements) or more common in squamous cell carcinoma (PIK3CA and AKT1 mutations).
Among our patients (48 men and 2 women) all adenocarcinoma (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding the tobacco risk threshold (at least 25 pack-years) and the women were none.
Nuclear extracts from H441 adenocarcinoma cells bound to the TTF-1 binding sites, were supershifted by anti-TTF-1 antibody, and were competed by other TTF-1 DNA binding motifs.
In this context, collagens (COL7, 17) and cytokeratins (CK6, 15, 17) are preferentially induced in squamous cell carcinoma, whereas several transcription factors (TTF1, DAT1, TF-2) are exclusively elevated in adenocarcinomas.
Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma.
MET overexpression was found more frequently in adenocarcinomas (and TTF1-positive tumors) and female patients and was also associated with expression of members of the epidermal growth factor receptor (EGFR) signaling cascade.
ROS1 expression was predominantly found in female adenocarcinoma patients, in patients with low T stages, and in association with TTF1 and napsin expression, and certain histomorphological adenocarcinoma patterns (lepidic, acinar, and solid).
After 12 mo of treatment with icotinib, ovarian biopsy showed adenocarcinoma with CDX2(-), TTF-1(+++), PAX8(-), CK-7(+++), CK-20(++), and Ki67(15%+), accompanied with EGFR 19-del mutation and T790M mutation.
These tumors displayed morphological characteristics of human pulmonary adenocarcinoma such as their epithelial origin, tubulo-acinar architecture and expression of TTF-1, SP-B and proSP-C.
In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung.
A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently.
In this study, we investigated 14 intestinal type OMNs (borderline and adenocarcinoma) and 12 endocervical-like OMNs (borderline and adenocarcinoma) for their expression of PDX-1, CDX-2, CA-125, CK7, CK20, WT-1, D2-40, and TTF-1.
When confined to stage IB adenocarcinomas with TTF-1-, whether received adjuvant chemotherapy made no difference to RFS and OS (RFS: <i>p</i> = 0.2707; OS: <i>p</i> = 1.000), as was the case in stage IB adenocarcinomas with TTF-1+ (RFS: <i>p</i> = 0.9161; OS: <i>p</i> = 0.1100).
Moreover, the regulation of TTF-1 gene expression described in this report is accompanied by the same regulation in its promoter activity, as demonstrated in transfection experiments performed in H-441 human lung-derived adenocarcinoma cells.
TTF-1 was expressed in a greater number of ACs (n=20; 95%), with lower mean expression levels, while the corresponding BM expressed the marker less frequently (n=16;76%) with higher mean expression values (p=0.011).P63 was expressed in all SCCs (p=0.68).