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

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; 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 (ASCL1, BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (NF1B). Formalin-fixed and paraffin-embedded sections of SCLC tumors were subjected to immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analyses. In a case-control cohort matched for basic clinical factors, expression of ProGRP, synaptophysin, chromogranin A, and ASCL1 was 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 significantly worse clinical outcomes were not observed.