Abstract
Tyroid transcription factor-1 (TTF-1) motivates the differentiation and development of bronchioloalveolar cells. The association of TTF-1 expression with prognosis in stage I adenocarcinoma is unclear. This study enrolled patients with resected stage I pulmonary adenocarcinoma who had TTF-1 immunostaining. All the corresponding clinicopathologic data including sex, age, smoking history, pathologic T stage, pathologic disease stage, surgical procedure, subtypes, follow-up records and adjuvant chemotherapy were investigated. Totally, 126 adenocarcinomas with TTF-1− and 2687 adenocarcinomas with TTF-1+ were subjected to the study. Among adenocarcinomas with TTF-1−, the major subtype was acinar-predominant adenocarcinomas, followed by invasive mucinous and papillary subtypes while acinar, papillary and minimally invasive adenocarcinoma were in the majority among adenocarcinomas with TTF-1+. The status of TTF-1 expression was not a significant factor for relapse-free survival (RFS) and overall survival (OS). Furthermore, there was no survival difference between the two groups (RFS: p = 0.2474; OS: p = 0.1480). When confined to stage IB adenocarcinomas with TTF-1−, whether received adjuvant chemotherapy made no difference to RFS and OS (RFS: p = 0.2707; OS: p = 1.000), as was the case in stage IB adenocarcinomas with TTF-1+ (RFS: p = 0.9161; OS: p = 0.1100). Within follow-up period, there was significant difference in post-recurrence survival (PRS) for TTF-1− patients compared with those TTF-1+ patients (Log-rank p = 0.0113). However, regarding to the recurrence site, there was no difference between TTF-1− patients and TTF-1+ patients in patients with stage I adenocarcinoma (p = 0.771) In conclusion, there is no significant difference in RFS and OS between TTF-1− group and TTF-1+ group, but TTF-1 negative adenocarcinoma has significantly worse PFS in patients with stage I adenocarcinoma. Moreover, chemotherapeutic efficacy between TTF-1+ and TTF-1− stage IB adenocarcinomas did not differ.
Highlights
Lung cancer remains the leading cause of cancer death worldwide in recent years [1]
2813 stage I patients including 126 adenocarcinomas with negative transcription factor-1 (TTF-1) expression and 2687 adenocarcinomas with positive TTF-1 expression were subjected to the study
As IASLC/American Thoracic Society (ATS)/European Respiratory Society (ERS) emphasized in the new classification in 2011, immunohistochemical, combined with histochemical and molecular studies were suggested to determine the specific type of lung cancer
Summary
Lung cancer remains the leading cause of cancer death worldwide in recent years [1]. Lung adenocarcinoma, accounting for nearly 50% of all lung cancer, is the most common histologic subtype and the morbidity rate is increasing year by year [2]. TTF-1, detecting in the immunohistochemistry www.impactjournals.com/oncotarget panel, acts as an important prognostic marker for diagnosis of lung adenocarcinoma, which was proposed by IASLC/ATS/ERS [3, 7,8,9]. Previous studies have demonstrated that positive TTF-1 expression (TTF-1+) is a significant prognostic factor for better outcome in pulmonary adenocarcinoma [11,12,13,14]. Some studies revealed the relationship between TTF-1 expression and gene mutations that a higher epidermal growth factor receptor (EGFR) mutation rate would be found in TTF-1 positive adenocarcinoma [15, 16]. The patients in their researches were commonly with advanced diseases and the chemotherapeutic effect between TTF-1 positive adenocarcinoma and TTF-1 negative adenocarcinoma, especially in early-stage lung adenocarcinoma is unknown. We undertook an investigation of TTF1 expression in stage I adenocarcinoma and compared the chemotherapeutic effect between TTF-1 positive adenocarcinoma and TTF-1 negative adenocarcinoma in pathological stage IB patients
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