Clinicopathological characteristics of thyroid transcription factor 1–negative small cell lung cancers

Summary Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer (NSCLC); however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (achaete-scute homolog like 1 (ASCL1), BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (Nuclear Factor 1B (NF1B)). Formalin-fixed and paraffin-embedded sections of SCLC tumors were subjected to immunohistochemistry and quantitative reverse transcription polymerase chain reaction (RT-PCR) analyses. In a case control cohort matched for basic clinical factors, expression of pro-gastrin-releasing peptide (ProGRP), synaptophysin, chromogranin A, and ASCL1 were significantly decreased in TTF-1-negative SCLC samples. In contrast, there was no significant correlation between Ki-67 labeling index and TTF-1. In a larger serial case cohort, TTF-1-negative SCLC cases were older at diagnosis but there was no significant difference in the overall survival of patients with TTF-1-negative and TTF-1-positive SCLC. In conclusion, TTF-1-negative SCLC showed decreased neuroendocrine differentiation, and significant worse clinical outcomes were not observed.