Aberrant expression of thyroid transcription factor–1 in schwannomas

• Published in: Human pathology 2018-01, Vol.71, p.84-90
• Main Authors: Wang, Dai-Zhong, Liu, Ping, Yao, Li, Hao, Ying-Hua, Zhu, Rui-Juan, Zhang, Tao, Tang, Xian-Bin
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - analysis; Brain cancer; DNA-Binding Proteins - biosynthesis; Gene expression; Genomes; Humans; Immunohistochemistry; Mesothelioma; mRNA; Nerve Sheath Neoplasms - pathology; Nervous system; Neurilemmoma - pathology; Proteins; qPCR; Retrospective Studies; Schwannoma; Thyroid gland; Transcription factors; Transcription Factors - biosynthesis; Transcriptional activation; TTF-1; Tumorigenesis; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2017.10.025

Aberrant expression of thyroid transcription factor-1 (TTF-1) has been observed in tumors arising in locations other than thyroid gland, lung and ventral forebrain. However, TTF-1 expression in schwannomas has not yet been studied. Meanwhile, a few inconsistent changes in protein expression have been identified between schwannomas and other peripheral nerve sheath tumors. We evaluated TTF-1 expression in 161 schwannomas and 43 other peripheral nervous system lesions, including ganglioneuromas (n = 8), malignant peripheral nerve sheath tumors (MPNSTs) (n = 11), neurofibromas (n = 24), and traumatic neuromas (n = 9), using immunohistochemistry and verified it using quantitative real-time reverse-transcription polymerase chain reaction (qPCR) to explore TTF-1 expression in peripheral nervous system lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained for both analyses. In this study, we observed nuclear TTF-1 staining in 109 (67.7%) schwannomas, including 102 of 131 (77.9%) conventional, 1 of 20 (5.0%) cellular and 6 of 10 (60.0%) plexiform schwannomas. Nuclear staining was not observed in normal peripheral nerves and non-schwannoma lesions. qPCR verified the aberrant expression and revealed a correlation between TTF-1 protein and mRNA levels (r = 0.633, P = .003). In conclusion, the data from our study show that TTF-1 is selectively expressed in the majority of schwannomas, particularly the conventional variants. Based on this observation, the TTF-1 protein and mRNA are specifically expressed in schwannomas. This highly aberrant expression of varying amounts of TTF-1 may provide new clues to reveal the pathogenesis of schwannoma. •TTF-1 was specially expressed in 68% of schwannomas.•A few cellular schwannomas expressed TTF-1.•All other peripheral nervous system lesions and the normal peripheral nervous tissues were TTF-1 negative.•The TTF-1 gene may be transcriptionally activated in schwannomas.