 |
Vol.61 No.2 contents | Japanese/English |
 | Full Text of PDF (3738K) Article in Japanese |
- Invited Review Article -
Transcription Factors and Regulators Involved in Cell Differentiation in Lung Tumor: Their Biological Significance and Role in the Pathological Diagnosis
Daisuke Matsubara11Division of Integrative Pathology, Jichi Medical University, Japan
In the pathological diagnosis of lung cancer, the expression of certain transcription factors is important as differentiation markers and for predicting underlying molecular abnormalities. TTF-1 is a master regulator of lung differentiation, and TTF-1-positive lung adenocarcinomas frequently harbor mutually exclusive driver mutations, such as EGFR and ALK. Furthermore, some studies have reported that TTF-1 itself is important for the survival of cancers. HNF4α, which is involved in gastrointestinal epithelial differentiation, is mutually exclusive with TTF-1 in lung cancer, and HNF4α-positive lung adenocarcinomas frequently harbor a TTF-1 gene-inactivating mutation/hypermethylation and KRAS mutation. SALL4, an embryonic tumor marker, is highly expressed in high-grade fetal adenocarcinoma. SALL4 is attracting attention as a new oncogene and a target for molecular therapy. In EMT-type lung cancer, the loss of chromatin remodeling factors, such as SMARCA4 and SMARCA2, has been observed, and in recent years, a new disease concept known as SMARCA4-deficient dedifferentiated tumor has been proposed. It was recently reported that small-cell carcinomas can be classified into four molecular subtypes depending on four transcription factors: ASCL1, NEUROD1, POU2F3, and YAP1. Based on my own pathological research on lung cancer, I will briefly explain these transcription factors and regulators related to the pathological diagnosis.
key words: Lung tumor, EMT, Neuroendocrine differentiation, YAP1, TTF-1, HNF4α, SMARCA4
JJLC 61 (2): 77-87, 2021
