Value of thyroid transcription factor (TTF)-1 for diagnosis and prognosis of patients with locally advanced or metastatic small cell lung cancer

Abstract

BackgroundThe aim of this study was to analyze the frequency of Thyroid Transcription Factor (TTF)-1 expression in small cell lung cancer (SCLC) and its value for the diagnosis of SCLC, the response to first line treatment as well as the prognostic impact on overall survival (OS).MethodsWe analyzed a total of 294 patients (m, n = 184; f, n = 110) with SCLC (stage IIIA, n = 32; IIIB, n = 87; IV, n = 175) diagnosed in our institution between January 2005 and December 2008. Patient’s characteristics comprising age, gender, histology and first line treatment were included into the analyses. For the follow-up of patients the governmental death registrar was used. The TTF-1 immunostaining was prospectively performed. CT scans of all patients were reviewed and response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors 1.0 (RECIST) criteria.ResultsA total of 221 of the 294 patients were eligible for analysis. Patients with TTF-1-positive SCLC had a median OS of 374 (95% CI 306–442) days. The OS of patients with TTF1-negative SCLC was 290 (95% CI 191–389) days, which was not significantly shorter (p = 0.254). Also stratification for tumor stage did not reveal significant difference in OS. Analyzing the disease control rate (DCR) in patients with metastatic disease (stage IV), we observed a significantly (p = 0.006) improved response to treatment in the group of patients with TTF-1-expression (DCR 86% vs. 56%). Regarding the overall response rates (ORR) in the entire population, there was no difference observed between both subgroups. (TTF-1-pos. 75.3% vs. TTF-1-neg. 71.4%; p = 0.642).ConclusionsThe diagnostic information of TTF-1 in SCLC seems to be limited. TTF-1 had no prognostic value concerning OS, but may serve as a predictor for response to first line chemotherapy.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5811254651472285

An integrative transcriptome analysis reveals a functional role for thyroid transcription factor‐1 in small cell lung cancer

“…Next, we performed immunohistochemistry for NFIB and TTF‐1 in tissue specimens from 12 SCLC patients (supplementary material, Table S5). Consistent with previous studies, strong staining of TTF‐1 was noted in eight tissue samples (67%) . All of the SCLC tissue samples were positive for NFIB, and co‐expression of NFIB and TTF‐1 in the nucleus of cancer cells was confirmed in TTF‐1‐positive SCLC cases (Figure B).…”

“…The prognostic impact of TTF‐1 immunoreactivity in SCLC cases remains unclear and previous studies failed to show statistically significant results, possibly due to the limited number of samples analysed . In this study, we explored whether the gene signature regulated by TTF‐1 could be associated with the prognosis of SCLC patients.…”

“…Expression of TTF‐1 is observed in about 70% of lung adenocarcinomas, and TTF‐1 is considered as a marker of the terminal respiratory unit (TRU) subtype . Although SCLC represents a prototypically undifferentiated cancer type, pathological studies have demonstrated that 80–90% of SCLC tissues are positive for TTF‐1 , suggesting a role of TTF‐1 other than promoting epithelial cell differentiation. This concept is supported by the notion that TTF‐1 is also expressed in small cell cancers of non‐pulmonary organs; for example, in the aggressive prostate cancer of small cell subtype .…”

Lineage transcription factors co-regulate subtype-specific genes providing a roadmap for systematic identification of small cell lung cancer vulnerabilities

“…NKX2-1 is also found in most SCLCs (61) where its SCLC expression correlates with that of ASCL1 (32,40). Our findings that ASCL1 and NKX2-1 interact and bind overlapping sites on the genome in SCLC are consistent with Hokari et al (2020).…”

Distinct prognostic roles and heterogeneity of TTF1 copy number and TTF1 protein expression in non‐small cell lung cancer

“…TTF1 plays a role in normal lung development and function (Kimura et al, ; Minoo et al, ). TTF1 is also expressed in the majority of lung adenocarcinoma (ADC) cases and approximately 80% of small‐cell lung cancer cases (Misch et al, ; Zhang et al, ). TTF1 functions as a lineage‐survival oncogene in lung cancer (Watanabe et al, ; Yamaguchi et al, ).…”