Despite the long life expectancy increase in non-small cell lung cancer (NSCLC) due to treatment with EGFR tyrosine kinase inhibitor drugs, brain metastases (BM) continue to be the most common cause of death. Lung adenocarcinoma (AC) is one of the most common malignancies that metastasizes to the brain, accounting for 40-60% of BM1.

TTF-1 is highly expressed in the basal cells of stratified squamous epithelia and gland epithelium in the terminal respiratory unit, which is responsible for oxygen-carbon dioxide exchange2. It is therefore used as an indicator of AC originating from this area of the respiratory tract3,4. Unlike p63, which is selectively expressed by proliferating cells, TTF-1 is expressed in normal squamous epithelia as well as in carcinomas, including adenocarcinoma.

In this study, TTF-1 was expressed in 78 of the 232 cases identified as small cell carcinoma on HFTSMA, and immunostaining results were available in 173 SCLC cases. The TTF-1 staining was considered negative if a diagnosis of SCLC was not unambiguously confirmed on pathologist review or if a mix of histologic types was observed (15 cases).

In the TTF-1-negative group, the majority of tumors were acinar predominate with some papillary and solid components. In comparison to the TTF1+ group, these patients presented with a higher rate of EGFR mutations and a lower overall survival. They also had a higher neoplastic grade and a larger tumor size than the TTF-1-positive group. In addition, TTF-1-negative patients did not show increased napsin A expression, which has been suggested as a marker of poor prognosis in ACs with wild-type EGFR.