Predictive significance of thyroid transcription factor-1 expression in patients with non‑squamous non-small cell lung cancer with wild-type epidermal growth factor receptor treated with erlotinib

Nakahara,Yoshiro; Hosomi,Yukio; Saito,Makoto; Ogawa,Masumi; Hishima,Tsunekazu; Okamura,Tatsuru; Sasaki,Jiichiro; Masuda,Noriyuki

doi:10.3892/mco.2016.870

Predictive significance of thyroid transcription factor-1 expression in patients with non‑squamous non-small cell lung cancer with wild-type epidermal growth factor receptor treated with erlotinib

Authors:
- Yoshiro Nakahara
- Yukio Hosomi
- Makoto Saito
- Masumi Ogawa
- Tsunekazu Hishima
- Tatsuru Okamura
- Jiichiro Sasaki
- Noriyuki Masuda
View Affiliations

Affiliations: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo 113‑8677, Japan, Department of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo 113‑8677, Japan, Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo 113‑8677, Japan, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0374, Japan, Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0374, Japan
Published online on: April 21, 2016 https://doi.org/10.3892/mco.2016.870
Pages: 14-18

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations

Abstract

Little is known on the efficacy of erlotinib treatment in patients expressing wild-type epidermal growth factor receptor (EGFR). This study is a retrospective review of patients with non‑squamous, non‑small‑cell lung cancer (NS‑NSCLC) and wild‑type EGFR who were treated with erlotinib alone as second- or later‑line chemotherapy at the Tokyo Metropolitan Cancer and Infectious Diseases Center of Komagome Hospital (Tokyo, Japan) between December, 2008 and December, 2013. Thyroid transcription factor‑1 (TTF-1) was immunohistochemically analyzed in 26 of 53 patients, among whom 20 (77%) and 6 (23%) were considered as TTF‑1‑positive and -negative, respectively. The median follow‑up of these 26 patients was 133 days (range, 26‑873 days). The time‑to‑treatment failure was significantly longer in TTF‑1‑positive compared with that in TTF‑1‑negative patients [49.5 vs. 20.0 days; 95% confidence interval (CI): 28‑90 vs. 14‑74 days, respectively; P=0.01]. The overall survival was significantly better for TTF‑1‑positive (227 days; 95% CI: 110‑366 days) compared with TTF-1-negative patients (P=0.0002). Therefore, the expression of TTF-1 may serve as a useful tool for predicting the efficacy of erlotinib in patients with NS-NSCLC expressing wild‑type EGFR.

View Figures

View References

1	Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI
2	Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, et al: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar : PubMed/NCBI
3	Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, et al: Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 12:735–742. 2011. View Article : Google Scholar : PubMed/NCBI
4	Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al: Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13:239–246. 2012. View Article : Google Scholar : PubMed/NCBI
5	Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, et al: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 353:123–132. 2005. View Article : Google Scholar : PubMed/NCBI
6	Myong NH: Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: Its prognostic implication and relationship with expressions of p53 and Ki-67 proteins. J Korean Med Sci. 18:494–500. 2003. View Article : Google Scholar : PubMed/NCBI
7	Tan D, Li Q, Deeb G, Ramnath N, Slocum HK, Brooks J, Cheney R, Wiseman S, Anderson T and Loewen G: Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: A high-throughput tissue microarray and immunohistochemistry study. Hum Pathol. 34:597–604. 2003. View Article : Google Scholar : PubMed/NCBI
8	Kubota K, Nishiwaki Y, Tamura T, Nakagawa K, Matsui K, Watanabe K, Hida T, Kawahara M, Katakami N, Takeda K, et al: Efficacy and safety of erlotinib monotherapy for Japanese patients with advanced non-small cell lung cancer: A phase II study. J Thorac Oncol. 3:1439–1445. 2008. View Article : Google Scholar : PubMed/NCBI
9	Berghmans T, Paesmans M, Mascaux C, Martin B, Meert AP, Haller A, Lafitte JJ and Sculier JP: Thyroid transcription factor 1 - a new prognostic factor in lung cancer: A meta-analysis. Ann Oncol. 17:1673–1676. 2006. View Article : Google Scholar : PubMed/NCBI
10	Grønberg BH, Lund-Iversen M, Strøm EH, Brustugun OT and Scott H: Associations between, TS and TTF-1, FR-α, FPGS, and overall survival in patients with advanced non-small-cell lung cancer receiving pemetrexed plus carboplatin or gemcitabine plus carboplatin as first-line chemotherapy. J Thorac Oncol. 8:1255–1264. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sun JM, Han J, Ahn JS, Park K and Ahn MJ: Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol. 6:1392–1399. 2011. View Article : Google Scholar : PubMed/NCBI