EGFR Mutations in Exons 18, 19 and 21 Are Closely Associated with TTF-1 Positive Lung Adenocarcinoma.
Ming Guo, Qiusheng Si, Yun Gong, Neda Kalhor, Su Chen, Cesar Moran. The Univerisity of Texas M.D. Anderson Cancer Center, Houton
Background: Molecular testing to detect EGFR and KRAS mutations are frequently utilized for targeted therapy in patients with non-small cell lung carcinoma, especially adenocarcinoma. Thyroid transcription factor 1 (TTF-1) positivity has been used as supportive evidence of primary lung adenocarcinoma or metastatic adenocarcinoma of lung origin. However, published data on the associations of EGFR or KRAS mutations with the TTF-1 status in lung adenocarcinoma is scant. In this study, we compared the EGFR and KRAS mutations in lung adenocarcinomas with positive or negative TTF-1 immunostain results.
Design: From our pathology data between January 2009 and June 2010, we identified 629 cases of lung adenocarcinoma with available EGFR and KRAS mutation results. The mean age of the patients was 64 years (range, 35-89). The results of EGFR or KRAS mutations detected by DNA sequencing were compared with TTF-1 status measured by immunostains in lung adenocarcinoma.
Results: Of the 629 adenocarcinomas, EGFR mutations were detected in 146 (23.2%), and KRAS mutations were observed in 147 (23.4%). Of the 344 adenocarcinomas that had TTF-1 results, 292 (85%) tumors were positive for TTF-1. The distribution of EGFR or KRAS mutations in adenocarcinomas with positive or negative TTF-1 results is listed in the Table 1. The frequencies of EGFR mutations were significantly higher in TTF-1-positive adenocarcinomas than those of TTF-1-negative adenocarcinomas (P = 0.016), specifically in exons 19 (44.7%, 34/76 vs. 0/76), 21 (40.1%, 31/76, vs. 1/4) and 18 (9.2%, 7/76 vs. 0/76). Significantly higher frequency of EGFR exon 20 mutation was detected in TTF-1-negative carcinomas (75%, 3/4) compared to that in the TTF-1- positive carcinomas (5%, 4/76) (P = 0.002). KRAS mutations were not significantly different between TTF-1-positive and TTF-1-negative adenocarcinomas (P = 0.314).
|TTF-1||Case No.||EGFR (%)||P-value||KRAS (%)||P-value|
|Positive||292||76 (26.0)||0.016||65 (22.3)||0.314|
|Negative||52||4 (7.7)||16 (30.8)|