Correlation between thyroid transcription factor, novel aspartic proteinase A expression and epidermal growth factor receptor, anaplastic lymphoma kinase gene mutation in lung adenocarcinoma

Abstract

Objective To investigate correlation between thyroid transcription factor-1 (TTF-1), novel aspartic proteinase A (Napsin A) expression and epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene mutation in lung adenocarcinoma. Methods A total of 227 patients with adenocarcinoma were collected in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2018. Immunohistochemistry was used to detect the expression of TTF-1 and Napsin A. The mutation of EGFR gene was detected by real-time fluorescent polymerase chain reaction or deoxyribonucleic acid sequencing. The mutations of ALK gene were detected by fluorescence in situ hybridization and enhanced immunohistochemistry. Results The positive rates of TTF-1 and Napsin A were 85.0% (193/227) and 76.4% (126/165), respectively. The mutation rate of ALK gene in TTF-1 and Napsin A negative patients was 0. The sensitivity, specificity of TTF-1 for predicting EGFR mutation were 97.8%(132/135), 33.7%(31/92), 68.4%(132/193) and 91.2%(31/34), respectively. The mutation rate of EGFR in TTF-1 positive patients was higher than that in negative patients (68.4% vs. 8.8%, P< 0.001). The expression of TTF-1 was not statistically correlated with ALK gene mutation (P=0.388). The sensitivity, specificity, positive predictive value and negative predictive value of Napsin A for predicting EGFR mutation were 94.4%(85/90), 45.3%(34/75), 67.5%(85/126) and 87.2%(34/39), respectively. The mutation rate of EGFR in Napsin A positive patients was higher than that in negative patients (67.5% vs. 12.8%, P<0.001). The expression of Napsin A was not statistically correlated with ALK gene mutation (P=0.199). The sensitivity, specificity of parallel test of TTF-1 and Napsin A for predicting EGFR mutation were 97.8%(88/90), 33.3%(25/75), respectively. The sensitivity, specificity of serial test of TTF-1 and Napsin A for predicting EGFR mutation were 68.5%(85/124), 87.8% (36/41), respectively. In both parallel test and serial test, the sensitivities of TTF-1 and Napsin A for predicting ALK gene mutation both were 100.0%(9/9), and the specificities were 17.0%(25/147), 25.2%(37/147), respectively. Conclusions EGFR gene mutation rate is higher in TTF-1 and Napsin A positive lung adenocarcinoma patients, and the expression of TTF-1 and Napsin A is not statistically correlated with ALK gene mutation. Key words: Lung adenocarcinoma; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Thyroid transcription factor-1; Novel aspartic proteinase A