TTF1negative

TTF1negative refers to a sample—typically a tissue biopsy or cell block—that does not express thyroid transcription factor‑1 (TTF‑1) when analyzed by immunohistochemistry. TTF‑1 is a nuclear protein encoded by the NKX2‑1 gene and is normally expressed in the epithelial cells of the thyroid gland, lungs, and parts of the central nervous system. It functions as a transcription factor regulating genes essential for organ development and maintenance. In pathology, TTF‑1 is a widely used biomarker to help identify the tissue of origin in carcinomas.

In practical terms, a TTF1negative result means that the tumor cells lack detectable nuclear staining for TTF‑1 under the microscope. This finding is typically interpreted as evidence that the tumor is unlikely to originate from a TTF‑1–positive site such as the lung or thyroid. For instance, in the workup of an undifferentiated carcinoma, a TTF1negative result would steer the diagnostic team toward non‑pulmonary or non‑thyroid primary sites.

TTF‑1 is used in a panel of immunostains that usually includes markers such as cytokeratin 7, cytokeratin 20, Napsin A, and others. Negative TTF‑1 can support diagnoses of metastatic adenocarcinomas from colorectal, pancreatic, or breast primaries, among others. However, the absence of TTF‑1 does not exclude a lung origin, because approximately 20–25 % of lung adenocarcinomas are TTF‑1 negative. Technical factors such as fixation, antigen retrieval, and antibody clone can also affect staining.

Clinicians and pathologists consider TTF1negative status alongside clinical information, imaging, and other histologic features to guide diagnosis, prognosis, and treatment decisions.