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).
The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification.
A total of 1244 NSCLC including 569 squamous cell carcinomas (SqCC) and 675 adenocarcinomas were assembled on a tissue microarray and stained with CK5/6, p40, p63, TTF-1, and Napsin-A.
As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas.
Positive protein expression of TTF1 (P=0.010) and CK7 (P=0.001) was significantly more prevalent in p-SQCC. p-SQCC had significantly higher gene expression of SPA (P=0.003), whereas c-SQCC showed higher gene expression of TP63 (P=0.028).
To improve segregation between ADC and SqCC in small samples, the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm.
The present study suggested that the combination of MUC5B and TTF-1 expression is useful for discriminating adenocarcinomas from squamous cell carcinomas, yielding prognostic significance in patients with lung adenocarcinoma.
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).
Ninety-five resected SQCCs, verified by immunohistochemistry as ΔNp63(+)/TTF-1(-), were tested for activating mutations in EGFR, KRAS, BRAF, PIK3CA, NRAS, AKT1, ERBB2/HER2, and MAP2K1/MEK1.
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.
We found TTF1 amplification in approximately 13% of adenocarcinomas (ACs) and in approximately 9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression.