## What is TTF-1?

Thyroid transcription factor 1 (TTF-1) is a homeodomain-containing nuclear transcription factor which belongs to the Nkx2 gene family; it is expressed in the forebrain, thyroid and lung. TTF-1 plays a key role in morphogenesis of the lungs[1] and is expressed in up to 90% of pulmonary small cell carcinoma[2].

## What is TTF-1 immunoreactivity in lung adenocarcinoma?

TTF-1, CK7 and CK20 lend themsleves to quantitative calculation of the probability that the tumour is metastatic. The frequency of TTF-1 immunoreactivity in extrapulmonary adenocarcinomas (excepting thyroid) is so low (1%) that positivity for TTF-1 may be interpreted as definite evidence that the tumour is a primary of lung.

**How common is TTF-1 expression in extrapulmonary small cell carcinoma?**

Agoff et al[7], Cheuk et al[15], Jones et al[16], Kaufmann et al[10], Li et al[17], Lu et al[18], McCluggage et al[19] and Yun et al[20] showed TTF-1 expression in 44%, 42%, 39%, 80%, 21%, 60%, 84% and 71% of extrapulmonary small cell cancers, respectively[7,10,15-20].

**What is the effect of TTF-1 negative and CK7 negative?**

It can be seen that the combination TTF-1 negative and CK7 negative gives a high modified probability of the tumour being metastatic, even when the prior probability is modest. It is also possible to calculate the proportions of tumours which will give each possible combination of results for any given prior probability.