1191P TTF-1 expression in lung neuroendocrine tumors (NET): A gender-related biomarker

Thyroid transcription factor-1 (TTF-1), is expressed in thyroid and lung tissue. TTF-1, assessed by immunohistochemistry (IHC), is a specific biomarker for lung adenocarcinoma, and is commonly used to confirm the pulmonary origin of neuroendocrine tumors (NET), as well. The majority of the available data suggest that TTF-1 is a favourable prognostic biomarker for lung adenocarcinomas, whereas its role in lung NET is controversial. A multicenter retrospective study, including 155 Lung NET, all surgically removed, all with available IHC assessment for TTF-1. Median age was 59.5 years (13–86), N= 58 patients (37.4%) were males, N=40 (25.8%) were smokers, N=31 (20%) were atypical carcinoids, N=85 (54.8%) were centrally-located, N=89 (57.4%) were located in the right lung, N=4 patients (2.6%) presented a TNM stage IV at the diagnosis. Mitotic count was ≥2 per 10 high-power field (HPF) in N=35 cases (22.6%), necrosis was present in N=20 (12.9%). Grade 1 was reported in 103 cases (66.5%), whereas Ki-67 was >20% in N=5 (3.2%). TTF-1 was positive in 78 cases (50.3%), cromogranin A in 139 (89.7%) and synaptophysin in 137 (88.4%), respectively. The most common type of surgery was lobectomy in 91 patients (58.7%). Median overall survival (OS) was 46.9 months (0.6–323), median progression-free survival (PFS) was 39.1 months (0.6–323). Statistically significant associations were found between (i) TTF-1 positivity and female sex (p=0.007), and among (ii) TTF-1 positivity and the absence of necrosis (p=0.018). No other relevant associations were detected between TTF-1 and the remaining clinical or pathological variables. This study highlights that TTF-1 positivity differs according to sex in lung NET patients, with a more common TTF-1 positive staining in female. Moreover, TTF-1 was associated with the absence of necrosis. These data suggest that TTF-1 could potentially represent a gender-related biomarker in this population. Further analyses are needed to establish the value of this observation, and to determine the value of TTF-1 as prognostic biomarker for lung NET.