P60.04 TTF1 Expression in Advanced Lung Adenocarcinoma and Survival Outcome: An Observational Study

Abstract

Prognosis of advanced lung adenocarcinoma remains poor despite significant advances in treatment options. Current literature calls for independent prognostic biomarkers to better stratify patient risk. Thyroid transcription factor 1 (TTF1) is regulatory protein that is suggested to be a favourable prognostic indicator independent of stage at diagnosis. The mechanism for this remains unclear with loss of differentiation of tumour a possible explanation. Further research, however, is needed for clinical application. This study explores TTF1 expression in adenocarcinoma of the lung and its correlation to survival outcomes as well as explores patterns of incidence in relation to tumour grade, gain of function mutations and PD-L1 status. This is a retrospective, observational, single-centre study of lung adenocarcinoma diagnosed between July 2017 and July 2020 in a large regional cancer centre in Victoria, Australia. Immunohistochemical reports and patient specific data were collected from patient records and analysed with simple descriptive statistics, binomial testing and Kaplan-Meier survival curves. A total of 86 adenocarcinoma of lung primary cases were identified (Age Range 49-89, Mean 69, ratio female to male 56%:44%). Of the total cases, 83% were TTF1 positive (n=71) and 13% negative (n=10). Gain of function mutations were present in 10.5% (n=9) of the cohort, with majority of these cases being TTF1 positive (78%, n=7). PD-L1 status analysis was completed in 44.7% of cases, with a majority being TTF1 positive (80% n=20). Overall, TTF1 negative tumours appeared more likely to be poorly differentiated (p=0.02), however TTF1 positive tumours did not have a significant association with well differentiated tumours (p=0.56). Overall, TTF1 positive tumours had a significantly longer survival compared to TTF1 negative tumours (median survival 64.7 weeks vs 9.4 weeks, on univariate analysis p<0.0004) . TTF1 positive tumours seem to have a longer overall survival regardless of their PD-L1 status, compared to the TTF1 negative group (p=0.04). TTF-1 expression in lung adenocarcinoma appears to be a good prognostic indicator regardless of PD-L1 status. Whilst TTF-1 negative status appears to be correlated with poorly differentiated tumours, positive TTF1 status does not necessarily reflect a degree of differentiation. These findings, are hypothesis generating and being planned to be validated in a larger cohort in a prospective manner, to define the clinical utility of TTF1 as a predictive/prognostic biomarker.